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Melanoma: HELP
Articles by Krishna L. Kanchi
Based on 2 articles published since 2008
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Between 2008 and 2019, Krishna L. Kanchi wrote the following 2 articles about Melanoma.
 
+ Citations + Abstracts
1 Article Inactivation of RASA1 promotes melanoma tumorigenesis via R-Ras activation. 2016

Sung, Hyeran / Kanchi, Krishna L / Wang, Xue / Hill, Kristen S / Messina, Jane L / Lee, Ji-Hyun / Kim, Youngchul / Dees, Nathan D / Ding, Li / Teer, Jamie K / Yang, Shengyu / Sarnaik, Amod A / Sondak, Vernon K / Mulé, James J / Wilson, Richard K / Weber, Jeffrey S / Kim, Minjung. ·Department of Molecular Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, FL, USA. · The Genome Institute, Washington University, St. Louis, MO, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA. · Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA. · Department of Medicine, Washington University, St. Louis, MO, USA. · Department of Genetics, Washington University, St. Louis, MO, USA. · Department of Tumor Biology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Medicine, NYU Langone Medical Center, New York, NY, USA. ·Oncotarget · Pubmed #26993606.

ABSTRACT: Inactivation of Ras GTPase activating proteins (RasGAPs) can activate Ras, increasing the risk for tumor development. Utilizing a melanoma whole genome sequencing (WGS) data from 13 patients, we identified two novel, clustered somatic missense mutations (Y472H and L481F) in RASA1 (RAS p21 protein activator 1, also called p120RasGAP). We have shown that wild type RASA1, but not identified mutants, suppresses soft agar colony formation and tumor growth of BRAF mutated melanoma cell lines via its RasGAP activity toward R-Ras (related RAS viral (r-ras) oncogene homolog) isoform. Moreover, R-Ras increased and RASA1 suppressed Ral-A activation among Ras downstream effectors. In addition to mutations, loss of RASA1 expression was frequently observed in metastatic melanoma samples on melanoma tissue microarray (TMA) and a low level of RASA1 mRNA expression was associated with decreased overall survival in melanoma patients with BRAF mutations. Thus, these data support that RASA1 is inactivated by mutation or by suppressed expression in melanoma and that RASA1 plays a tumor suppressive role by inhibiting R-Ras, a previously less appreciated member of the Ras small GTPases.

2 Article Clonal architectures and driver mutations in metastatic melanomas. 2014

Ding, Li / Kim, Minjung / Kanchi, Krishna L / Dees, Nathan D / Lu, Charles / Griffith, Malachi / Fenstermacher, David / Sung, Hyeran / Miller, Christopher A / Goetz, Brian / Wendl, Michael C / Griffith, Obi / Cornelius, Lynn A / Linette, Gerald P / McMichael, Joshua F / Sondak, Vernon K / Fields, Ryan C / Ley, Timothy J / Mulé, James J / Wilson, Richard K / Weber, Jeffrey S. ·The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Genetics, Washington University in St. Louis, St. Louis, Missouri, United States of America; Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, United States of America. · Donald A. Adam Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida, United States of America. · The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America. · The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Genetics, Washington University in St. Louis, St. Louis, Missouri, United States of America. · Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, United States of America. · The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America. · Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, United States of America. · Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America; Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, United States of America. · Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, United States of America. · The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America; Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, United States of America. · The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Genetics, Washington University in St. Louis, St. Louis, Missouri, United States of America; Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, United States of America. ·PLoS One · Pubmed #25393105.

ABSTRACT: To reveal the clonal architecture of melanoma and associated driver mutations, whole genome sequencing (WGS) and targeted extension sequencing were used to characterize 124 melanoma cases. Significantly mutated gene analysis using 13 WGS cases and 15 additional paired extension cases identified known melanoma genes such as BRAF, NRAS, and CDKN2A, as well as a novel gene EPHA3, previously implicated in other cancer types. Extension studies using tumors from another 96 patients discovered a large number of truncation mutations in tumor suppressors (TP53 and RB1), protein phosphatases (e.g., PTEN, PTPRB, PTPRD, and PTPRT), as well as chromatin remodeling genes (e.g., ASXL3, MLL2, and ARID2). Deep sequencing of mutations revealed subclones in the majority of metastatic tumors from 13 WGS cases. Validated mutations from 12 out of 13 WGS patients exhibited a predominant UV signature characterized by a high frequency of C->T transitions occurring at the 3' base of dipyrimidine sequences while one patient (MEL9) with a hypermutator phenotype lacked this signature. Strikingly, a subclonal mutation signature analysis revealed that the founding clone in MEL9 exhibited UV signature but the secondary clone did not, suggesting different mutational mechanisms for two clonal populations from the same tumor. Further analysis of four metastases from different geographic locations in 2 melanoma cases revealed phylogenetic relationships and highlighted the genetic alterations responsible for differential drug resistance among metastatic tumors. Our study suggests that clonal evaluation is crucial for understanding tumor etiology and drug resistance in melanoma.