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Melanoma: HELP
Articles by Colleen M. Cebulla
Based on 15 articles published since 2008
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Between 2008 and 2019, Colleen M. Cebulla wrote the following 15 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Ocular melanoma and the BAP1 hereditary cancer syndrome: implications for the dermatologist. 2014

Martorano, Lisa M / Winkelmann, Richard R / Cebulla, Colleen M / Abdel-Rahman, Mohamed H / Campbell, Shannon M. ·Richmond Medical Center, University Hospitals, Cleveland, OH, USA. ·Int J Dermatol · Pubmed #24697775.

ABSTRACT: Ocular melanoma is a rare subtype of melanoma, which includes uveal melanoma (UM) and conjunctival melanoma. UM is associated with an increased risk of cutaneous melanoma (CM) in addition to mesothelioma, skin lesions such as epithelioid atypical Spitz tumors, and other internal malignancies due to a germline mutation of the BRCA1-associated protein 1 (BAP1) gene. Such familial risks are important for dermatologists to recognize when screening patients with a history of UM for CM and other malignancies. Molecular genetics further help to elucidate the connections between UM and CM by revealing similarities and differences in important mutations among the melanoma subtypes. Both UM and CM have been shown to harbor germline mutation of BAP1. However, somatic mutations in either GNAQ or GNA11 are unique to UM tumors and could be used as potential markers to differentiate UM from metastatic CM and act as direct therapeutic targets. However, CM-associated BRAF and CDKN2A mutations are rare in UM. This review addresses the clinical features, pathogenesis, and current treatment options of UM, focusing on UM and the BAP1 cancer syndrome to raise awareness of ocular melanoma and its greater role in the predisposition to a hereditary cancer syndrome.

2 Article Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. 2017

Robertson, A Gordon / Shih, Juliann / Yau, Christina / Gibb, Ewan A / Oba, Junna / Mungall, Karen L / Hess, Julian M / Uzunangelov, Vladislav / Walter, Vonn / Danilova, Ludmila / Lichtenberg, Tara M / Kucherlapati, Melanie / Kimes, Patrick K / Tang, Ming / Penson, Alexander / Babur, Ozgun / Akbani, Rehan / Bristow, Christopher A / Hoadley, Katherine A / Iype, Lisa / Chang, Matthew T / Anonymous1031111 / Cherniack, Andrew D / Benz, Christopher / Mills, Gordon B / Verhaak, Roel G W / Griewank, Klaus G / Felau, Ina / Zenklusen, Jean C / Gershenwald, Jeffrey E / Schoenfield, Lynn / Lazar, Alexander J / Abdel-Rahman, Mohamed H / Roman-Roman, Sergio / Stern, Marc-Henri / Cebulla, Colleen M / Williams, Michelle D / Jager, Martine J / Coupland, Sarah E / Esmaeli, Bita / Kandoth, Cyriac / Woodman, Scott E. ·Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada. · The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. · Buck Institute for Research on Aging, Novato, CA 94945, USA. · Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. · Department of Biomolecular Engineering, Center for Biomolecular Sciences and Engineering, University of California, Santa Cruz, CA 95064, USA. · Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Public Health Sciences, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA. · The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21287, USA. · The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA. · Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA. · Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. · Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Human Oncology and Pathogenesis Program, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. · Molecular and Medical Genetics, Computational Biology, Oregon Health and Science University, Portland, OR 97239, USA. · Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Institute for Applied Cancer Science, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. · Institute for Systems Biology, Seattle, WA 98109, USA. · Human Oncology and Pathogenesis Program, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Departments of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94122, USA. · Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Dermatology, University Hospital Essen, 45157 Essen, Germany. · Center for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Pathology, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA. · Department of Pathology, Dermatology and Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Departments of Ophthalmology and Internal Medicine, Division of Human Genetics, The Ohio State University, Columbus, OH 43210, USA. · Department of Translational Research, Institut Curie, PSL Research University, Paris 75248, France. · Havener Eye Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43212, USA. · Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. · Department of Molecular & Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool L7 8TX, UK; Department of Cellular Pathology, Royal Liverpool University Hospital, Liverpool, L69 3GA, UK. · Orbital Oncology & Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: besmaeli@mdanderson.org. · Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. Electronic address: kandothc@mskcc.org. · Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: swoodman@mdanderson.org. ·Cancer Cell · Pubmed #28810145.

ABSTRACT: Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

3 Article Germline BAP1 alterations in familial uveal melanoma. 2017

Rai, Karan / Pilarski, Robert / Boru, Getachew / Rehman, Muneeb / Saqr, Ahmad H / Massengill, James B / Singh, Arun / Marino, Meghan J / Davidorf, Frederick H / Cebulla, Colleen M / H Abdel-Rahman, Mohamed. ·Division of Human Genetics, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. · Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Columbus, Ohio. · Cole Eye Institute, Department of Ophthalmic Oncology, Cleveland Clinic, Cleveland, Ohio. ·Genes Chromosomes Cancer · Pubmed #27718540.

ABSTRACT: Uveal melanoma (UM) is the most commonly diagnosed primary intraocular tumor in adults. Familial UM (FUM), defined as two or more family members diagnosed with UM, is rare and estimated at less than 1% of all UM. Currently, BAP1 is the only gene known to contribute significant risk for UM. In this study we aimed to estimate the frequency of BAP1 mutation in FUM and to characterize the family and personal histories of other cancers in these families. We identified 32 families with FUM, including seven families previously reported by our group. BAP1 mutation testing was carried out by direct sequencing of the coding exons and the adjacent untranslated regions of the gene. Germline deletion and duplication analysis of BAP1 was assessed by multiplex ligation-dependent probe amplification (MLPA). Germline BAP1 mutations were found in 6/32 (19%) families. No deletions or duplications were identified in any of the 24 samples tested by MLPA. Combined with published studies, the frequency of BAP1 mutations was 14/64 (22%) in FUM. FUM families without BAP1 mutations have distinct family histories with high rates of prostate cancer in first- and second-degree relatives. It is likely that additional genes conferring risk for FUM exist. It is important to understand key shared features of FUM to focus future research on identifying these additional tumor predisposition syndromes. Though BAP1 should be tested first in these families, FUM families without BAP1 mutation should be explored for additional predisposition genes. © 2016 Wiley Periodicals, Inc.

4 Article Genetic markers of pigmentation are novel risk loci for uveal melanoma. 2016

Ferguson, Robert / Vogelsang, Matjaz / Ucisik-Akkaya, Esma / Rai, Karan / Pilarski, Robert / Martinez, Carlos N / Rendleman, Justin / Kazlow, Esther / Nagdimov, Khagay / Osman, Iman / Klein, Robert J / Davidorf, Frederick H / Cebulla, Colleen M / Abdel-Rahman, Mohamed H / Kirchhoff, Tomas. ·Perlmutter Cancer Center, New York University School of Medicine, New York, USA. · Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, USA. · The Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, USA. · Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. · Department of Medicine, New York University School of Medicine, New York, USA. · Ronald O. Perelman, Department of Dermatology, New York University, New York, USA. · Department of Genetic and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. · Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH USA. ·Sci Rep · Pubmed #27499155.

ABSTRACT: While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR = 0.529, 95% CI 0.415-0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419-0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339-0.637; p = 3.04E-07) are correlated (r(2) > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility.

5 Article Germline BAP1 mutations misreported as somatic based on tumor-only testing. 2016

Abdel-Rahman, Mohamed H / Rai, Karan / Pilarski, Robert / Davidorf, Frederick H / Cebulla, Colleen M. ·Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH, USA. mohamed.abdel-rahman@osumc.edu. · Division of Human Genetics, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. mohamed.abdel-rahman@osumc.edu. · Department of Pathology, Menoufiya University, Shebin El-Kom, Egypt. mohamed.abdel-rahman@osumc.edu. · Division of Human Genetics, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. · Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, OH, USA. ·Fam Cancer · Pubmed #26748926.

ABSTRACT: We present three unrelated patients with germline mutations in BAP1 misreported as somatic mutations. All had strong family histories of cancer. One of these patients presented with an invasive breast cancer with the tumor tissue showing partial loss of the mutant rather than the wild type allele, suggesting that the germline BAP1 mutation didn't contribute to breast cancer development in this patient. This data highlights the importance of sequencing matching germline and tumor DNA for proper assessment of somatic versus germline mutation status. In patients with somatic mutations reported from laboratories carrying out tumor-only genomic testing, the possibility that a variant may be a germline mutation should be considered, especially if the personal and/or family history suggests hereditary cancer predisposition. Since tumor-only testing can reveal germline mutations, ethical issues for patients being tested should be considered including proper consent and genetic counseling.

6 Article Long-term visual acuity outcomes in patients with uveal melanoma treated with 125I episcleral OSU-Nag plaque brachytherapy. 2016

Wisely, C Ellis / Hadziahmetovic, Mersiha / Reem, Rachel E / Hade, Erinn M / Nag, Subir / Davidorf, Frederick H / Martin, Douglas / Cebulla, Colleen M. ·Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University Wexner Medical Center, Columbus, OH. · Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH. · Center for Biostatistics, Department of Bioinformatics, The Ohio State University Wexner Medical Center, Columbus, OH. · Department of Radiation Oncology, Northern California Kaiser Permanente, Santa Clara, CA. · Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address: Douglas.Martin@osumc.edu. ·Brachytherapy · Pubmed #26525215.

ABSTRACT: PURPOSE: To report our experience in long-term follow-up of ocular melanoma patients treated with custom OSU-Nag eye plaques using (125)I sources. METHODS: A retrospective chart review was conducted for 113 consecutive ocular melanoma patients with follow-up visual acuity data who were treated with OSU-Nag plaque episcleral brachytherapy at The Ohio State University Medical Center from 1994 to 2009. Visual acuity, complication data, and recurrence rates were recorded up to 120 months after brachytherapy. RESULTS: Median age at presentation was 63.0 years (range, 22-93). Median follow-up was 65.5 months (range, 2-180). Median radiation dose at the prescription point was 85.8 Gy (range, 51.8-103.7). Preservation of useful visual acuity, defined as better than 20/200, was noted in 43 of 74 (58%) of patients in the present study at 36 months compared with 50.1% of Collaborative Ocular Melanoma Study participants. By 120 months, 17 of 30 (57%; 95% confidence interval, 45-69%) progressed to visual acuity worse than 20/200, whereas 9 of 30 (30%) retained visual acuity of 20/40 or better, and 4 of 30 (13%) were 20/50-20/200. The rate of retinopathy after radiation was approximately 40% of all those observed by 60 months. Baseline visual acuity, apical tumor height, American Joint Committee on Cancer tumor category, and distance between the tumor and the fovea were all significantly associated with loss of visual acuity. The local tumor control rate by 60 months of follow-up was 93% (95% confidence interval, 85-97%). CONCLUSIONS: The OSU-Nag custom (125)I plaque is an effective treatment for uveal melanoma, with preservation of useful visual acuity in 58% of eyes 3 years after treatment and 43% of eyes 10 years after treatment.

7 Article Bilateral Choroidopathy and Serous Retinal Detachments During Ipilimumab Treatment for Cutaneous Melanoma. 2015

Mantopoulos, Dimosthenis / Kendra, Kari L / Letson, Alan D / Cebulla, Colleen M. ·Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Wexner Medical Center, Columbus. · Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Wexner Medical Center, Columbus. ·JAMA Ophthalmol · Pubmed #25974108.

ABSTRACT: -- No abstract --

8 Article Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients. 2015

Cebulla, Colleen M / Binkley, Elaine M / Pilarski, Robert / Massengill, James B / Rai, Karan / Liebner, David A / Marino, Meghan J / Singh, Arun D / Abdel-Rahman, Mohamed H. ·Havener Eye Institute, Department of Ophthalmology and Visual Science . ·Ophthalmic Genet · Pubmed #25687217.

ABSTRACT: BACKGROUND: To evaluate the prevalence of BAP1 germline mutations in a series of young patients with uveal melanoma (UM), diagnosed before age 30. MATERIALS AND METHODS: The study was carried out on 14 young uveal melanoma patients (average age 21.4 years, range 3 months to 29 years). Germline DNA was extracted from peripheral blood. BAP1 sequencing was carried out using direct sequencing of all exons and adjacent intronic sequences. We also tested for germline mutations in additional melanoma-associated candidate genes CDKN2A and CDK4 (exon 4). RESULTS: We identified one patient with a pathogenic mutation (c. 1717delC, p.L573fs*3) in BAP1. This patient was diagnosed with UM at age 18 years and had a family history of a father with UM and a paternal grandfather with cancer of unknown origin. One additional patient had an intronic variant of uncertain significance (c.123-48T > G) in BAP1 while the remaining 12 patients had no alteration. None of the patients had CDKN2A or CDK4 (Exon 4) mutations. Family history was positive for a number of additional malignancies in this series, in particular for cutaneous melanoma, prostate, breast and colon cancers. There were no families with a history of mesothelioma or renal cell carcinoma. CONCLUSIONS: This study suggests that a small subset of patients with early onset UM has germline mutation in BAP1. While young patients with UM should be screened for germline BAP1 mutations, our results suggest that there is a need to identify other candidate genes which are responsible for UM in young patients.

9 Article Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases. 2014

Pilarski, Robert / Cebulla, Colleen M / Massengill, James B / Rai, Karan / Rich, Thereasa / Strong, Louise / McGillivray, Barbara / Asrat, Mary-Jill / Davidorf, Frederick H / Abdel-Rahman, Mohamed H. ·Division of Human Genetics, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. ·Genes Chromosomes Cancer · Pubmed #24243779.

ABSTRACT: The clinical phenotype of BAP1 hereditary cancer predisposition syndrome (MIM 614327) includes uveal melanoma (UM), cutaneous melanoma (CM), renal cell carcinoma (RCC), and mesothelioma. However, the frequency of the syndrome in patients with UM and the association with other cancers are still not clear. In this study, we screened 46 previously untested, unrelated UM patients with high risk for hereditary cancer for germline mutation in BAP1. We also studied four additional patients with a personal or family history suggestive of BAP1 hereditary cancer syndrome. We identified three patients with germline pathogenic mutations (c.2050 C>T, pGln684*; c.1182C>G, p.Tyr394*, and c.1882_1885delTCAC, p. Ser628Profs*8) in BAP1. Two of these three patients presented with UM and the third with a metastatic adenocarcinoma likely from a hepatic cholangiocarcinoma. Reported family histories included UM, mesothelioma, RCC, CM, and several other internal malignancies. The results of this study confirm the association between germline BAP1 mutation and predisposition to UM, mesothelioma, CM and RCC. However, other cancers, such as cholangiocarcinoma and breast carcinoma may be part of the phenotype of this hereditary cancer predisposition syndrome. In addition, the results support the existence of other candidate genes in addition to BAP1 contributing to hereditary predisposition to UM.

10 Article Monosomy 3 status of uveal melanoma metastases is associated with rapidly progressive tumors and short survival. 2012

Abdel-Rahman, Mohamed H / Cebulla, Colleen M / Verma, Vishal / Christopher, Benjamin N / Carson, William E / Olencki, Thomas / Davidorf, Frederick H. ·Department of Ophthalmology, The Ohio State University, Columbus, OH 43210, USA. Mohamed.abdel-rahman@osumc.edu ·Exp Eye Res · Pubmed #22569040.

ABSTRACT: The aim of the study was to investigate the molecular genetics of uveal melanoma (UM) metastases and correlate it with disease progression. Twelve pathologically confirmed UM metastases from 11 patients were included. Molecular genetic alterations in chromosomes 3 (including the BAP1 region), 8q, 6p, and 1p were investigated by microsatellite genotyping. Mutations in codon 209 of GNAQ and GNA11 genes were studied by restriction-fragment length polymorphism (RFLP). We identified monosomy of chromosome 3 in tumors from four patients with an average survival of 5 months (range 1-8 months) from time of diagnosis of metastatic disease. In contrast, tumors with either disomy or partial chromosome 3 alterations showed significantly slower metastatic disease progression with an average survival of 69 months (range 40-123 months, p = 0.003). Alterations in chromosomal arms 1p, 6p, and 8q and mutations in either GNAQ or GNA11 showed no association with disease progression. Prominent mononuclear inflammatory infiltrate was observed in tumors from patients with slowly progressive disease. In conclusion, in UM metastases, monosomy 3 is associated with highly aggressive, rapidly progressive disease while disomy or partial change of 3 and prominent mononuclear inflammatory infiltrate in the tumor is associated with better prognosis. These findings should be considered when designing clinical trials testing effectiveness of various therapies of metastatic UM.

11 Article Molecular genetic testing of uveal melanoma from routinely processed and stained cytology specimens. 2011

Christopher, Benjamin N / Cebulla, Colleen M / Wakely, Paul E / Davidorf, Frederick H / Abdel-Rahman, Mohamed H. ·Department of Ophthalmology, The Ohio State University, Columbus, OH, USA. ·Exp Eye Res · Pubmed #21945171.

ABSTRACT: In the following study we investigated the utility of molecular genetic testing of the DNA extracted from routinely stained and processed smears from uveal melanoma (UM). Smears from five uveal melanoma cell lines and 12 primary tumors were prepared and stained with Papanicolaou and Romanowsky stains. Genotyping was carried out utilizing 14 microsatellite markers on chromosomes 3, 6 and 8. Mutational screening for alterations in GNAQ and GNA11 genes was carried out by restriction fragment length polymorphism. The results were compared to those obtained through direct sequencing of frozen tumor tissues. High quality DNA was extracted from the stained slides with no difference in the efficiency of DNA extraction between the two staining techniques. The extracted DNA was of adequate quality for genotyping and mutational screening. DNA extracted from approximately 200 tumor cells is sufficient for reproducible testing of allelic imbalances and for studying the common somatic mutations in GNAQ and GNA11 genes. In conclusion, we presented the feasibility of utilizing routinely stained cytology smears from UM for molecular genetic testing. The DNA obtained is of sufficient quality to carry out genotyping for markers on chromosome 3, 6 and 8, as well as screening for somatic mutations in GNAQ and GNA11 genes.

12 Article Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. 2011

Abdel-Rahman, Mohamed H / Pilarski, Robert / Cebulla, Colleen M / Massengill, James B / Christopher, Benjamin N / Boru, Getachew / Hovland, Peter / Davidorf, Frederick H. ·Department of Ophthalmology, The Ohio State University, Columbus, Ohio, USA. mohamed.abdel-rahman@osumc.edu ·J Med Genet · Pubmed #21941004.

ABSTRACT: OBJECTIVE: To investigate the potential contribution of germline sequence alterations in the BAP1 gene in uveal melanoma (UM) patients with possible predisposition to hereditary cancer. DESIGN: A total of 53 unrelated UM patients with high risk for hereditary cancer and five additional family members of one proband were studied. Mutational screening was carried out by direct sequencing. RESULTS: Of the 53 UM patients studied, a single patient was identified with a germline BAP1 truncating mutation, c. 799 C→T (p.Q267X), which segregated in several family members and was associated with UM and other cancers. Biallelic inactivation of BAP1 and decreased BAP1 expression were identified in the UM, lung adenocarcinoma and meningioma tumours from three family members with this germline BAP1 mutation. Germline BAP1 variants of uncertain significance, likely non-pathogenic, were also identified in two additional UM patients. CONCLUSION: This study reports a novel hereditary cancer syndrome caused by a germline BAP1 mutation that predisposes patients to UM, lung carcinoma, meningioma, and possibly other cancers. The results indicate that BAP1 is the candidate gene in only a small subset of hereditary UM, suggesting the contribution of other candidate genes.

13 Article Blood vessel maturation in human uveal melanoma: spatial distribution of neovessels and mature vasculature. 2009

Piña, Yolanda / Cebulla, Colleen M / Murray, Timothy G / Alegret, Armando / Dubovy, Sander R / Boutrid, Hinda / Feuer, William / Mutapcic, Lejla / Jockovich, Maria-Elena. ·Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Fla 33101, USA. ·Ophthalmic Res · Pubmed #19321938.

ABSTRACT: PURPOSE: The aims of this study are (1) to evaluate the spatial distribution of neovessels and mature vessels in human uveal melanoma tumors and (2) to determine whether vessel maturation is associated with the major indicators for poor prognosis. METHODS: Immunohistochemical analyses were performed on human tissue specimens from enucleated eyes (n = 14) to assess total vessels, neovessels, mature vessels, and cell proliferation. Tumor morphology was analyzed by hematoxylin and eosin and modified periodic acid-Schiff (PAS) staining.The spatial distribution of neovessels and mature vessels was analyzed by immunohistochemistry, and correlated with major indicators of poor prognosis (i.e., aggressive PAS patterns, epithelioid cytology, mitotic figures, extraocular extension, anterior tumor location, ciliary body involvement, large tumor size, cell proliferation, and angiogenic activity). RESULTS: Neovesseldensity was greater than mature vessel density in apical (p = 0.17), central (p = 0.036), and peripheral (p = 0.31) regions of the tumors, while mature vessel density was greater than neovessel density in basal areas of the tumor (p = 0.47). This pattern indicated that vessel maturation begins at the base of the tumor and later extends to the peripheral and apical regions. The difference between mature and neovessel densities for the apical (-0.8 +/- 1.9) and central areas (-0.8 +/- 1.3) of the tumor was significantly higher than the difference obtained for the basal area (0.3 +/- 1.6; p = 0.014 and p = 0.012, respectively), indicating a higher density of mature vessels compared to neovessels at the base. Statistical correlations were found between mature vessel density and tumor size (r = 0.48, p = 0.084), cell proliferation (r = 0.62, p = 0.042), and mitotic figures (r = 0.76, p = 0.001). CONCLUSIONS: Significant differences exist in the spatial distribution of mature versus neovessels in human uveal melanoma. Vessel maturation is associated with known clinical and pathologic indicators of poor prognosis (e.g., cell proliferation). Antiangiogenic therapy should be considered for the treatment of ocular malignancies; however, the results of this study indicate that blood vessel maturation heterogeneity may limit the efficacy of vessel targeting agents.

14 Article Tumor volume reduction using combined phacoemulsification and intravitreal triamcinolone injection for the management of cataract with treated uveal melanoma and atypical nevi. 2008

Cebulla, Colleen M / Alegret, Armando M / Feuer, William J / Shi, Wei / Schefler, Amy C / Murray, Timothy G. ·Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida 33101, USA. ·J Cataract Refract Surg · Pubmed #18812116.

ABSTRACT: PURPOSE: To study the reduction in tumor size and the safety and efficacy of combined phacoemulsification and intravitreal triamcinolone acetonide injection (phaco-IVTA) in patients with treated melanoma and atypical nevi. SETTING: Bascom Palmer Eye Institute, Miami, Florida, USA. METHODS: The medical records of 49 consecutive patients (51 eyes) with treated melanoma or atypical nevi treated with phaco-IVTA were evaluated retrospectively for changes in Snellen visual acuity, tumor volume, and frequency of complications. Main outcome measures included a postsurgical change in tumor size greater than or equal to 0.5 mm of height or 1.0 mm of basal diameter by echographic analysis, improvement in visual acuity at 6 months and final follow-up, and complications including endophthalmitis, cystoid macular edema, epiretinal membrane, increased intraocular pressure, and persistent corneal edema. RESULTS: The median baseline visual acuity was 20/80 in the affected eye. At the 6-month follow-up examination, 13 (68%) of 19 eyes had achieved better than 20/40 visual acuity. Treated uveal melanomas (n=30) and atypical choroidal nevi (n=21) were stable with combined therapy, and echographic measurements improved in 12 eyes. Intraocular pressure increased from baseline to 25 mm Hg or more postoperatively in 4 of 51 eyes (8%). No other significant complications occurred. CONCLUSIONS: Combined phacoemulsification and IVTA was reasonably safe in patients with treated melanoma and atypical nevi. Tumors remained stable or decreased slightly in size. Intravitreal triamcinolone acetonide injection at the time of cataract surgery in patients with treated melanoma or nevus may reduce rates of tumor progression in these patients.

15 Minor Optic disc edema from remote uveal melanoma. 2013

Clark, Sireesha A / Lubow, Martin / Ray-Chaudhury, Abhik / Davidorf, Frederick H / Abdel-Rahman, Mohamed H / Cebulla, Colleen M. · ·JAMA Ophthalmol · Pubmed #23307225.

ABSTRACT: -- No abstract --