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Melanoma: HELP
Articles by Alberto S. Pappo
Based on 17 articles published since 2008
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Between 2008 and 2019, A. Pappo wrote the following 17 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Pediatric melanoma: the whole (genome) story. 2014

Pappo, Alberto S. ·From the Solid Tumor Division, St. Jude Children's Research Hospital, Memphis, TN. ·Am Soc Clin Oncol Educ Book · Pubmed #24857134.

ABSTRACT: Pediatric melanoma is rare and given the diagnostic challenges it presents in this age group, it is difficult to interpret the literature describing its natural history and outcome. Recent genomic analysis demonstrates that conventional melanoma in children and adolescents shares many of the genomic features that have been described in adult melanoma, including BRAF mutations. Thus, this patient group should be given the opportunity to enroll in National Cancer Institute and pharmaceutically sponsored trials that incorporate novel targeted agents.

2 Review Management of melanomas in children and young adults. 2012

Neier, Michelle / Pappo, Alberto / Navid, Fariba. ·Valerie Fund Center, Goryeb Children's Hospital, Morristown, NJ 07962, USA. Michelle.Neier@atlantichealth.org ·J Pediatr Hematol Oncol · Pubmed #22525407.

ABSTRACT: Melanoma is rare in children and young adults. The incidence is rising yearly in this population. The clinical features of the disease in the pediatric population have been well documented through single-institution experiences and population-based analyses. Still, our understanding of the etiologic factors in the majority of children remains unclear, and diagnosis of melanoma remains challenging in certain cases. Because of its rarity, the staging, management and treatment of melanoma in this population is adopted from adult guidelines. In this review, we provide information on the epidemiology, clinical presentation, staging, prognosis and management of melanoma in children and young adults.

3 Clinical Trial Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma. 2017

Geoerger, Birgit / Bergeron, Christophe / Gore, Lia / Sender, Leonard / Dunkel, Ira J / Herzog, Cynthia / Brochez, Lieve / Cruz, Ofelia / Nysom, Karsten / Berghorn, Elmer / Simsek, Burcin / Shen, Jun / Pappo, Alberto. ·Gustave Roussy, Université Paris-Saclay, Department of Pediatric and Adolescent Oncology, Villejuif, France. Electronic address: Birgit.GEOERGER@gustaveroussy.fr. · Institut D'Hematologie et D'Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France. · University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA. · University of California, Irvine School of Medicine, Orange, CA, USA. · Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. · University of Texas, MD Anderson Cancer Center, Houston, TX, USA. · Ghent University Hospital, Ghent, Belgium. · Hospital Sant Joan de Déu Barcelona, Barcelona, Spain. · Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. · Bristol-Myers Squibb, Princeton, NJ, USA. · St. Jude Children's Research Hospital, Memphis, TN, USA. ·Eur J Cancer · Pubmed #29100190.

ABSTRACT: BACKGROUND: Ipilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available. METHODS: Patients aged 12 to <18 years with previously treated or untreated, unresectable stage III or IV malignant melanoma received ipilimumab 3 or 10 mg/kg every 3 weeks. Primary end-points were 1-year overall survival and safety. RESULTS: Over a period of 3.5 years, 12 patients received ipilimumab at either 3 mg/kg (n = 4) or 10 mg/kg (n = 8). The median number of ipilimumab doses was four for 3 mg/kg and three for 10 mg/kg. At 1 year, three of four patients on 3 mg/kg and five of eight patients on 10 mg/kg were alive. Two patients on 10 mg/kg had partial response, and one on 3 mg/kg had stable disease. One patient had durable partial response at 3 years without further treatment, at time of this report. There was one grade 3/4 immune-mediated adverse reaction with 3 mg/kg and five with 10 mg/kg. There were no treatment-related deaths. The study was stopped due to slow accrual. CONCLUSIONS: At >1 year follow-up, ipilimumab demonstrated activity in melanoma patients aged 12 to <18 years, with a similar safety profile as that seen in adults. Our trial highlights the difficulties of enrolling younger patients with rare diseases in clinical trials for treatments that are approved in adults, suggesting adolescents with cancer types occurring predominantly in adults should be considered for inclusion in adult trials of promising new drugs. CLINICAL TRIAL REGISTRATION: NCT01696045.

4 Clinical Trial Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E1697). 2017

Agarwala, Sanjiv S / Lee, Sandra J / Yip, Waiki / Rao, Uma N / Tarhini, Ahmad A / Cohen, Gary I / Reintgen, Douglas S / Evans, Terry L / Brell, Joanna M / Albertini, Mark R / Atkins, Michael B / Dakhil, Shaker R / Conry, Robert M / Sosman, Jeffrey A / Flaherty, Lawrence E / Sondak, Vernon K / Carson, William E / Smylie, Michael G / Pappo, Alberto S / Kefford, Richard F / Kirkwood, John M. ·Sanjiv S. Agarwala, Saint Luke's University Hospital, Easton · Uma N. Rao, Ahmad A. Tarhini, Terry L. Evans, and John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA · Sandra J. Lee, and Waiki Yip, Dana Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA · Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD · Douglas S. Reintgen, Lakeland Regional Cancer Center, Lakeland · Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL · Joanna M. Brell, MetroHealth Medical Center, Cleveland · William E. Carson, The Ohio State University Comprehensive Cancer Center, Columbus, OH · Mark R. Albertini, University of Wisconsin Hospital, Madison, WI · Michael B. Atkins, Georgetown Medical Center, Washington, DC · Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS · Robert M. Conry, University of Alabama at Birmingham, Birmingham, AL · Jeffrey A. Sosman, Vanderbilt University, Nashville · Alberto S. Pappo, Saint Jude Children's Research Hospital Oncology, Memphis, TN · Lawrence E. Flaherty, Wayne State University/Karmanos Cancer Institute, Detroit, MI · Michael G. Smylie, Cross Cancer Institute, Edmonton, Canada · and Richard F. Kefford, Sydney West Area Health Service, Westmead, Australia. ·J Clin Oncol · Pubmed #28135150.

ABSTRACT: Purpose To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma. Patients and Methods In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m

5 Clinical Trial Feasibility of Pegylated Interferon in Children and Young Adults With Resected High-Risk Melanoma. 2016

Navid, Fariba / Herzog, Cynthia E / Sandoval, John / Daryani, Vinay M / Stewart, Clinton F / Gattuso, Jami / Mandrell, Belinda / Phipps, Sean / Chemaitilly, Wassim / Sykes, April / Davidoff, Andrew M / Shulkin, Barry L / Bahrami, Armita / Furman, Wayne L / Mao, Shenghua / Wu, Jianrong / Schiff, Deborah / Rao, Bhaskar / Pappo, Alberto. ·Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee. · Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas. · Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee. · Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Nursing Research, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Pediatric Medicine, Division of Endocrinology, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Pediatrics, University of California-San Diego, La Jolla, California. ·Pediatr Blood Cancer · Pubmed #27038395.

ABSTRACT: BACKGROUND: Pegylated interferon α-2b (IFN α-2b) improves disease-free survival in adults with resected stage III melanoma. We conducted a study to determine the feasibility and safety of incorporating pegylated IFN α-2b as adjuvant therapy in the treatment of children and adolescents with high-risk melanoma. Pharmacokinetic studies of IFN α-2b and neuropsychological and quality of life (OL) assessments were performed. PATIENT AND METHODS: Eligible patients with resected American Joint Committee on Cancer Stage IIC, IIIA, and IIIB cutaneous melanoma received nonpegylated IFN α-2b 20 million units/m(2) /day intravenously 5 days per week for 4 weeks (induction) followed by pegylated IFN α-2b 1 μg/kg/dose weekly subcutaneously (SQ) for 48 weeks (maintenance). RESULTS: Twenty-three patients (15 females, median age 10 years) were enrolled. All patients completed induction therapy; five patients did not complete maintenance therapy either because of recurrent disease (n = 2) or toxicity (n = 3). The most common grade 3 and 4 toxicities of pegylated IFN α-2b were neutropenia (35%) and elevated liver transaminases (17%). The median nonpegylated IFN α-2b AUC0-∞ (5,026 pcg⋅hr/ml) was similar to adults. The median pegylated IFN α-2b exposure (48,480 pcg⋅hr/ml) was greater than the cumulative weekly exposure for nonpegylated IFN α-2b administered SQ three times per week (TIW). Validated measures demonstrated an improvement in QOL scores and no decline in psychological functioning over the course of therapy. CONCLUSIONS: Pegylated IFN α-2b 1 μg/kg/dose SQ weekly as maintenance therapy in children and adolescents with high-risk melanoma is feasible with tolerable toxicity and appears to yield higher exposures than nonpegylated IFN α-2b administered SQ TIW.

6 Clinical Trial Southwest Oncology Group S0008: a phase III trial of high-dose interferon Alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma--an intergroup study of cancer and leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. 2014

Flaherty, Lawrence E / Othus, Megan / Atkins, Michael B / Tuthill, Ralph J / Thompson, John A / Vetto, John T / Haluska, Frank G / Pappo, Alberto S / Sosman, Jeffrey A / Redman, Bruce G / Moon, James / Ribas, Antoni / Kirkwood, John M / Sondak, Vernon K. ·Lawrence E. Flaherty, Wayne State University, Detroit · Bruce G. Redman, University of Michigan, Ann Arbor, MI · Megan Othus, James Moon, Southwest Oncology Group Statistical Center · John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA · Michael B. Atkins, Georgetown University Hospital, Washington DC · Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH · John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR · Frank G. Haluska, Tufts-New England Medical Center, Boston, MA · Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX · Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN · Antoni Ribas, University of California Los Angeles, Los Angeles, CA · John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA · Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL. ·J Clin Oncol · Pubmed #25332243.

ABSTRACT: PURPOSE: High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective. PATIENTS AND METHODS: S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS). RESULTS: In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms. CONCLUSION: Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.

7 Article Clinical genome sequencing uncovers potentially targetable truncations and fusions of MAP3K8 in spitzoid and other melanomas. 2019

Newman, Scott / Fan, Liying / Pribnow, Allison / Silkov, Antonina / Rice, Stephen V / Lee, Seungjae / Shao, Ying / Shaner, Bridget / Mulder, Heather / Nakitandwe, Joy / Shurtleff, Sheila / Azzato, Elizabeth M / Wu, Gang / Zhou, Xin / Barnhill, Raymond / Easton, John / Nichols, Kim E / Ellison, David W / Downing, James R / Pappo, Alberto / Potter, Philip M / Zhang, Jinghui / Bahrami, Armita. ·Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. scott.newman@stjude.org. · Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA. · Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. · Department of Pediatrics, Division of Hematology/Oncology, Stanford University School of Medicine, Palo Alto, CA, USA. · Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. · Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. · Departments of Pathology and Translational Research, Institute Curie, Paris, France. · Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. jinghui.zhang@stjude.org. · Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. armita.bahrami@stjude.org. · Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. armita.bahrami@stjude.org. ·Nat Med · Pubmed #30833747.

ABSTRACT: Spitzoid melanoma is a specific morphologic variant of melanoma that most commonly affects children and adolescents, and ranges on the spectrum of malignancy from low grade to overtly malignant. These tumors are generally driven by fusions of ALK, RET, NTRK1/3, MET, ROS1 and BRAF

8 Article The role of routine imaging in pediatric cutaneous melanoma. 2018

Halalsheh, Hadeel / Kaste, Sue C / Navid, Fariba / Bahrami, Armita / Shulkin, Barry L / Rao, Bhaskar / Kunkel, Michelle / Artz, Nathan / Pappo, Alberto. ·Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee. · Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, Tennessee. · Department of Radiology, University of Tennessee School of Health Science, Tennessee. · Division of Hematology, Oncology and Bone Marrow Transplant, Children's Hospital Los Angeles, California. · Keck School of Medicine, University of Southern California, Los Angeles, California. · Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee. · Department of Surgery, St Jude Children's Research Hospital, Memphis, Tennessee. · Cancer Center Administration, St Jude Children's Research Hospital, Memphis, Tennessee. ·Pediatr Blood Cancer · Pubmed #30124237.

ABSTRACT: BACKGROUND: Optimal imaging for children with pediatric malignant melanoma (MM) is unknown. METHODS: We reviewed clinical and imaging findings of patients with American Joint Commission on Cancer (AJCC) stage IIC-IV MM treated on our institutional MEL06 trial. All patients had baseline brain magnetic resonance imaging/computed tomography (MRI/CT), positron emission tomography/computed tomography (PET/CT), CT chest, abdomen, and pelvis (CTCAP). Patients on stratum A (PEG-interferon, where PEG is pegylated; AJCC IIC, IIIA, IIIB; n = 16) had imaging every 6 months; stratum B1 (PEG-interferon and temozolomide; unresectable measurable disease, metastatic, or recurrent; n = 2) had PET/CT scans every 2 months and brain imaging studies every 4 months; stratum B2 patients (PEG-interferon and temozolomide; unresectable nonmeasurable, metastatic, or recurrent, n = 3) had imaging every 4 months. Off-therapy imaging was done every 6 months for 3 years. RESULTS: There were 21 patients (11 females, 11 spitzoid, median age 14 years, head/neck [6], trunk [7], extremities [8]). Patients with spitzoid melanoma underwent 236 imaging studies in total (86 PET/CT, 81 CTCAP, 11 CT chest, 10 CT brain, 48 MRI brain) at a median cost per patient of $32,718. Thirteen studies (5.8%) had findings that led to two biopsies (one positive). For conventional MM, 162 studies (61 PET/CT, 57 CTCAP, 8 CT chest, 7 CT brain, and 29 MRI brain) were performed with a median cost per patient of $23,420. Twenty (14%) had findings leading to six biopsies (four positive). At 6.3 years (range 0.4-9.2), 17 patients remain disease-free. CONCLUSION: Children with spitzoid melanoma require minimal imaging at diagnosis and follow-up. Patients with conventional MM should be imaged according to adult guidelines.

9 Article Genetic and Epigenetic Alterations of TERT Are Associated with Inferior Outcome in Adolescent and Young Adult Patients with Melanoma. 2017

Seynnaeve, Brittani / Lee, Seungjae / Borah, Sumit / Park, Yongseok / Pappo, Alberto / Kirkwood, John M / Bahrami, Armita. ·Department of Pediatric Hematology/Oncology, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224, USA. · Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. · Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. · Department of Oncology, St. Jude Children's Research Hospital, Memphis Tennessee 38105, USA. · Department of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. ·Sci Rep · Pubmed #28378855.

ABSTRACT: Progression of melanoma to distant sites in adolescents and young adults (AYAs) is not reliably predicted by clinicopathologic criteria. TERT promoter mutations when combined with BRAF/NRAS mutations correlate with adverse outcome in adult melanoma. To determine the prognostic value of TERT alterations in AYA melanoma, we investigated the association of TERT promoter mutations, as well as promoter methylation, an epigenetic alteration also linked to TERT upregulation, with TERT mRNA expression and outcome using a well-characterized cohort of 27 patients with melanoma (ages 8-25, mean 20). TERT mRNA expression levels were significantly higher in tumors harboring TERT promoter mutation and/or hypermethylation than those without either aberration (P = 0.046). TERT promoter mutations alone did not predict adverse outcomes (P = 0.50), but the presence of TERT promoter methylation, alone or concurrent with promoter mutations, correlated with reduced recurrence-free survival (P = 0.001). These data suggest that genetic and epigenetic alterations of TERT are associated with TERT upregulation and may predict clinical outcomes in AYA melanoma. A more exhaustive understanding of the different molecular mechanisms leading to increased TERT expression may guide development of prognostic assays to stratify AYA melanoma patients according to clinical risk.

10 Article The landscape of fusion transcripts in spitzoid melanoma and biologically indeterminate spitzoid tumors by RNA sequencing. 2016

Wu, Gang / Barnhill, Raymond L / Lee, Seungjae / Li, Yongjin / Shao, Ying / Easton, John / Dalton, James / Zhang, Jinghui / Pappo, Alberto / Bahrami, Armita. ·Department of Computational Biology, St Jude Children's Research Hospital, Memphis, TN, USA. · Department of Pathology, Institute Curie, and Faculty of Medicine, University of Paris Descartes, Paris, France. · Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA. · Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. ·Mod Pathol · Pubmed #26892443.

ABSTRACT: Kinase activation by chromosomal translocations is a common mechanism that drives tumorigenesis in spitzoid neoplasms. To explore the landscape of fusion transcripts in these tumors, we performed whole-transcriptome sequencing using formalin-fixed, paraffin-embedded (FFPE) tissues in malignant or biologically indeterminate spitzoid tumors from 7 patients (age 2-14 years). RNA sequence libraries enriched for coding regions were prepared and the sequencing was analyzed by a novel assembly-based algorithm designed for detecting complex fusions. In addition, tumor samples were screened for hotspot TERT promoter mutations, and telomerase expression was assessed by TERT mRNA in situ hybridization (ISH). Two patients had widespread metastasis and subsequently died of disease, and 5 patients had a benign clinical course on limited follow-up (mean: 30 months). RNA sequencing and TERT mRNA ISH were successful in six tumors and unsuccessful in one disseminating tumor because of low RNA quality. RNA sequencing identified a kinase fusion in five of the six sequenced tumors: TPM3-NTRK1 (2 tumors), complex rearrangements involving TPM3, ALK, and IL6R (1 tumor), BAIAP2L1-BRAF (1 tumor), and EML4-BRAF (1 disseminating tumor). All predicted chimeric transcripts were expressed at high levels and contained the intact kinase domain. In addition, two tumors each contained a second fusion gene, ARID1B-SNX9 or PTPRZ1-NFAM1. The detected chimeric genes were validated by home-brew break-apart or fusion fluorescence in situ hybridization (FISH). The two disseminating tumors each harbored the TERT promoter -124C>T (Chr 5:1,295,228 hg19 coordinate) mutation, whereas the remaining five tumors retained the wild-type gene. The presence of the -124C>T mutation correlated with telomerase expression by TERT mRNA ISH. In summary, we demonstrated complex fusion transcripts and novel partner genes for BRAF by RNA sequencing of FFPE samples. The diversity of gene fusions demonstrated by RNA sequencing defines the molecular heterogeneity of spitzoid neoplasms.

11 Article The Childhood Solid Tumor Network: A new resource for the developmental biology and oncology research communities. 2016

Stewart, Elizabeth / Federico, Sara / Karlstrom, Asa / Shelat, Anang / Sablauer, Andras / Pappo, Alberto / Dyer, Michael A. ·Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. · Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. · Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. · Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. · Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: michael.dyer@stjude.org. ·Dev Biol · Pubmed #26068307.

ABSTRACT: Significant advances have been made over the past 25 years in our understanding of the most common adult solid tumors such as breast, colon, lung and prostate cancer. Much less is known about childhood solid tumors because they are rare and because they originate in developing organs during fetal development, childhood and adolescence. It can be very difficult to study the cellular origins of pediatric solid tumors in developing organs characterized by rapid proliferative expansion, growth factor signaling, developmental angiogenesis, programmed cell death, tissue reorganization and cell migration. Not only has the etiology of pediatric cancer remained elusive because of their developmental origins, but it also makes it more difficult to treat. Molecular targeted therapeutics that alter developmental pathway signaling may have devastating effects on normal organ development. Therefore, basic research focused on the mechanisms of development provides an essential foundation for pediatric solid tumor translational research. In this article, we describe new resources available for the developmental biology and oncology research communities. In a companion paper, we present the detailed characterization of an orthotopic xenograft of a pediatric solid tumor derived from sympathoadrenal lineage during development.

12 Article The genomic landscape of childhood and adolescent melanoma. 2015

Lu, Charles / Zhang, Jinghui / Nagahawatte, Panduka / Easton, John / Lee, Seungjae / Liu, Zhifa / Ding, Li / Wyczalkowski, Matthew A / Valentine, Marcus / Navid, Fariba / Mulder, Heather / Tatevossian, Ruth G / Dalton, James / Davenport, James / Yin, Zhirong / Edmonson, Michael / Rusch, Michael / Wu, Gang / Li, Yongjin / Parker, Matthew / Hedlund, Erin / Shurtleff, Sheila / Raimondi, Susana / Bhavin, Vadodaria / Donald, Yergeau / Mardis, Elaine R / Wilson, Richard K / Evans, William E / Ellison, David W / Pounds, Stanley / Dyer, Michael / Downing, James R / Pappo, Alberto / Bahrami, Armita. ·The Genome Institute, Washington University School of Medicine in St Louis, St Louis, Missouri, USA. · Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. · Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. · Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee, USA. · The Genome Institute, Washington University School of Medicine in St Louis, St Louis, Missouri, USA; Department of Genetics, Washington University School of Medicine in St Louis, St Louis, Missouri, USA; Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA; Siteman Cancer Center, Washington University School of Medicine in St Louis, St Louis, Missouri, USA. · Department of Cytogenetics, St Jude Children's Research Hospital, Memphis, Tennessee, USA. · Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. · Department of Genetics, Washington University School of Medicine in St Louis, St Louis, Missouri, USA; Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA; Siteman Cancer Center, Washington University School of Medicine in St Louis, St Louis, Missouri, USA. · Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA. · Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. Electronic address: alberto.pappo@stjude.org. · Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. Electronic address: armita.bahrami@stjude.org. ·J Invest Dermatol · Pubmed #25268584.

ABSTRACT: Despite remarkable advances in the genomic characterization of adult melanoma, the molecular pathogenesis of pediatric melanoma remains largely unknown. We analyzed 15 conventional melanomas (CMs), 3 melanomas arising in congenital nevi (CNMs), and 5 spitzoid melanomas (SMs), using various platforms, including whole genome or exome sequencing, the molecular inversion probe assay, and/or targeted sequencing. CMs demonstrated a high burden of somatic single-nucleotide variations (SNVs), with each case containing a TERT promoter (TERT-p) mutation, 13/15 containing an activating BRAF V600 mutation, and >80% of the identified SNVs consistent with UV damage. In contrast, the three CNMs contained an activating NRAS Q61 mutation and no TERT-p mutations. SMs were characterized by chromosomal rearrangements resulting in activated kinase signaling in 40%, and an absence of TERT-p mutations, except for the one SM that succumbed to hematogenous metastasis. We conclude that pediatric CM has a very similar UV-induced mutational spectrum to that found in the adult counterpart, emphasizing the need to promote sun protection practices in early life and to improve access to therapeutic agents being explored in adults in young patients. In contrast, the pathogenesis of CNM appears to be distinct. TERT-p mutations may identify the rare subset of spitzoid melanocytic lesions prone to disseminate.

13 Article Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: a report from the childhood cancer survivor study. 2013

Pappo, A S / Armstrong, G T / Liu, W / Srivastava, D K / McDonald, A / Leisenring, W M / Hammond, S / Stovall, M / Neglia, J P / Robison, L L. ·Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. alberto.pappo@stjude.org ·Pediatr Blood Cancer · Pubmed #22887858.

ABSTRACT: BACKGROUND: Childhood cancer survivors have a sixfold increased risk of developing subsequent neoplasms when compared to the general population. We sought to describe the occurrence of melanoma as a subsequent neoplasm among adult survivors of childhood cancer. PATIENTS AND METHODS: Among 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, we calculated the cumulative incidence, standardized incidence ratio (SIR), and absolute excess risk (AER) of subsequent melanoma. Potential risk factors were assessed using a cause-specific hazards model. RESULTS: Fifty-seven melanomas (46 invasive, 2 ocular, and 9 in situ) occurred in 51 survivors. The median time to the development of melanoma was 21.0 years (range: 5.6-35.4 years) and the median age at melanoma was 32.3 years (range: 10.9-49.0 years). Initial cancer diagnoses included soft tissue and bone sarcoma (n = 15), leukemia (13), lymphoma (14), central nervous system malignancy (5), Wilms tumor (3), and neuroblastoma (1). The cumulative incidence of first subsequent melanoma at 35 years from initial cancer diagnosis was 0.55% [95% confidence interval (CI): 0.37-0.73]. The SIR of subsequent invasive malignant melanoma of the skin was 2.42 (95% CI: 1.77-3.23), and the AER was 0.10 (95% CI: 0.05-0.15) per 1,000 person-years. No statistically significant associations were found between melanoma risk and family history of cancer, demographic, or treatment-related factors. CONCLUSION: Survivors of childhood cancer have an approximate 2.5-fold increased risk of melanoma. Early screening and prevention strategies are warranted.

14 Article Increased detection of metastatic melanoma in pediatric sentinel lymph node biopsies using RT-PCR on paraffin-embedded tissue. 2010

Somers, Gino R / Chilton-MacNeill, Susan / Zheng, Keqin / Stuart, Mary / Pappo, Alberto / Zielenska, Maria / Thorner, Paul S. ·Department of Paediatric Laboratory Medicine, Hospital for Sick Children, University of Toronto, ON, Canada. gino.somers@sickkids.ca ·Appl Immunohistochem Mol Morphol · Pubmed #20571343.

ABSTRACT: Sentinel lymph node (SLN) biopsy has become integral in the staging of patients with melanoma, and entails detailed histologic examination with immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase transcripts has been used to increase sensitivity but requires a dedicated piece of tissue that does not undergo histologic examination. We developed a nested RT-PCR assay for tyrosinase applicable on paraffin-embedded tissue and applied this to a series of SLNs from pediatric patients with melanoma. Thirty-six SLNs from 4 females and 4 males were included in the study. Eight lymph nodes with reactive changes were included as controls. SLNs were examined histologically and immunohistochemically for S100, tyrosinase, and MART1. Seven patients had between 1 and 4 morphologically-positive SLNs and one patient had negative SLNs (HISTO+; 12/36, 33%). Three lymph nodes were excluded from molecular analysis owing to inadequate RNA, and 29 of the remaining 33 nodes were positive (MOL+; 88%). All patients had at least 1 SLN positive by RT-PCR. Twelve were HISTO+/MOL+; 17 were HISTO-/MOL+; and 4 were HISTO-/MOL-. All control lymph nodes were negative for tyrosinase transcripts. The application of RT-PCR for tyrosinase to paraffin-embedded tissue significantly increased the number of positive SLNs and upstaged one patient from negative to positive. The prognostic implications of such findings require further investigation, especially in the pediatric age group. Nonetheless, this technique provides a useful tool to determine the clinical significance of RT-PCR positivity in melanoma SLNs.

15 Article Administration of high-dose interleukin-2 in a 2-year-old with metastatic melanoma. 2009

Bernhardt, M Brooke / Hicks, M John / Pappo, Alberto S. ·Department of Pharmacy, Texas Children's Hospital, Houston, Texas 77030, USA. mbbernha@texaschildrens.org ·Pediatr Blood Cancer · Pubmed #19731326.

ABSTRACT: Malignant melanoma is rare in pediatrics, and therapies for patients with disseminated disease have not been well studied. This report describes our experience with the use of high-dose interleukin 2 (aldesleukin, IL-2) in a 2-year-old child with metastatic melanoma and describes our approach for the administration of this agent to young patients.

16 Minor Association of TERT promoter mutations with telomerase expression in melanoma. 2016

Lee, Seungjae / Opresko, Patricia / Pappo, Alberto / Kirkwood, John M / Bahrami, Armita. ·Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. · Department of Environmental and Occupational Health, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. · Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. · Division of Hematology-Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. ·Pigment Cell Melanoma Res · Pubmed #26928778.

ABSTRACT: -- No abstract --

17 Minor Telomerase Expression by Aberrant Methylation of the TERT Promoter in Melanoma Arising in Giant Congenital Nevi. 2016

Fan, Yiping / Lee, Seungjae / Wu, Gang / Easton, John / Yergeau, Donald / Dummer, Reinhard / Vogel, Peter / Kirkwood, John M / Barnhill, Raymond L / Pappo, Alberto / Bahrami, Armita. ·Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. · Division of Hematology-Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Departement of Pathology, Institute Curie, Paris, France. · Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. · Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee. Electronic address: armita.bahrami@stjude.org. ·J Invest Dermatol · Pubmed #26763461.

ABSTRACT: -- No abstract --