Cargando…
Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience
BACKGROUND: Primary mutations in the KIT gene are the driving force for gastrointestinal stromal tumors (GIST) tumorigenesis. Predictive role of KIT mutation status aids oncologists in patient management. There is a paucity of comprehensive data on the frequency of mutations in the KIT gene in GIST...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615879/ https://www.ncbi.nlm.nih.gov/pubmed/28975118 http://dx.doi.org/10.4103/sajc.sajc_275_16 |
_version_ | 1783266682048872448 |
---|---|
author | Pai, Trupti Bal, Munita Shetty, Omshree Gurav, Mamta Ostwal, Vikas Ramaswamy, Anant Ramadwar, Mukta Desai, Sangeeta |
author_facet | Pai, Trupti Bal, Munita Shetty, Omshree Gurav, Mamta Ostwal, Vikas Ramaswamy, Anant Ramadwar, Mukta Desai, Sangeeta |
author_sort | Pai, Trupti |
collection | PubMed |
description | BACKGROUND: Primary mutations in the KIT gene are the driving force for gastrointestinal stromal tumors (GIST) tumorigenesis. Predictive role of KIT mutation status aids oncologists in patient management. There is a paucity of comprehensive data on the frequency of mutations in the KIT gene in GIST affecting Indian patients. The aims of this study were to determine the frequency and spectrum of molecular alterations affecting the KIT gene and assess their association with clinicopathologic features in a cohort of patients of GIST. MATERIALS AND METHODS: Morphological and immunohistochemically confirmed GIST cases (n = 114) accessioned from August 2014-June 2015 were analyzed for mutations in KIT exons 9, 11, 13, and 17 and subjected to Sanger sequencing onto the ABI 3500 Genetic Analyzer. The sequences were analyzed using sequence analysis software: SeqScape(®) and Chromas Lite. RESULTS: KIT mutations were seen in 70% of cases and the majority of KIT mutations involved exon 11 (57%), followed by exon 9 (10%), exon 13 (3%), and exon 17 (1%). Most common exon 11 mutations were in-frame deletions (61.4%) followed by substitution mutations (19.3%). Exon 9 mutations showed identical duplication of Ala-Tyr at codons 502–503. Simultaneous mutations affecting exon 11 and 13 were discovered. Novel variations, namely, p.Q556E (c.1666C>G), p.Q556dup (c.1666_1668dupCAG), p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT), p.Y503_F504insTY (c.1509_1510insACCTAT), and p.K642R (c.1925A>G) involving exons 11, 9, and 13, respectively, were observed. INTERPRETATION AND CONCLUSIONS: First study with complete analysis of all 4 exons of KIT (exons 9, 11, 13, and 17) in Indian GIST patients. Along with well-described KIT mutations, several rare double mutations as well as novel alterations were reported in this series. |
format | Online Article Text |
id | pubmed-5615879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-56158792017-10-03 Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience Pai, Trupti Bal, Munita Shetty, Omshree Gurav, Mamta Ostwal, Vikas Ramaswamy, Anant Ramadwar, Mukta Desai, Sangeeta South Asian J Cancer ORIGINAL ARTICLE: GI Cancer BACKGROUND: Primary mutations in the KIT gene are the driving force for gastrointestinal stromal tumors (GIST) tumorigenesis. Predictive role of KIT mutation status aids oncologists in patient management. There is a paucity of comprehensive data on the frequency of mutations in the KIT gene in GIST affecting Indian patients. The aims of this study were to determine the frequency and spectrum of molecular alterations affecting the KIT gene and assess their association with clinicopathologic features in a cohort of patients of GIST. MATERIALS AND METHODS: Morphological and immunohistochemically confirmed GIST cases (n = 114) accessioned from August 2014-June 2015 were analyzed for mutations in KIT exons 9, 11, 13, and 17 and subjected to Sanger sequencing onto the ABI 3500 Genetic Analyzer. The sequences were analyzed using sequence analysis software: SeqScape(®) and Chromas Lite. RESULTS: KIT mutations were seen in 70% of cases and the majority of KIT mutations involved exon 11 (57%), followed by exon 9 (10%), exon 13 (3%), and exon 17 (1%). Most common exon 11 mutations were in-frame deletions (61.4%) followed by substitution mutations (19.3%). Exon 9 mutations showed identical duplication of Ala-Tyr at codons 502–503. Simultaneous mutations affecting exon 11 and 13 were discovered. Novel variations, namely, p.Q556E (c.1666C>G), p.Q556dup (c.1666_1668dupCAG), p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT), p.Y503_F504insTY (c.1509_1510insACCTAT), and p.K642R (c.1925A>G) involving exons 11, 9, and 13, respectively, were observed. INTERPRETATION AND CONCLUSIONS: First study with complete analysis of all 4 exons of KIT (exons 9, 11, 13, and 17) in Indian GIST patients. Along with well-described KIT mutations, several rare double mutations as well as novel alterations were reported in this series. Medknow Publications & Media Pvt Ltd 2017 /pmc/articles/PMC5615879/ /pubmed/28975118 http://dx.doi.org/10.4103/sajc.sajc_275_16 Text en Copyright: © 2017 The South Asian Journal of Cancer http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | ORIGINAL ARTICLE: GI Cancer Pai, Trupti Bal, Munita Shetty, Omshree Gurav, Mamta Ostwal, Vikas Ramaswamy, Anant Ramadwar, Mukta Desai, Sangeeta Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience |
title | Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience |
title_full | Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience |
title_fullStr | Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience |
title_full_unstemmed | Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience |
title_short | Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience |
title_sort | unraveling the spectrum of kit mutations in gastrointestinal stromal tumors: an indian tertiary cancer center experience |
topic | ORIGINAL ARTICLE: GI Cancer |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615879/ https://www.ncbi.nlm.nih.gov/pubmed/28975118 http://dx.doi.org/10.4103/sajc.sajc_275_16 |
work_keys_str_mv | AT paitrupti unravelingthespectrumofkitmutationsingastrointestinalstromaltumorsanindiantertiarycancercenterexperience AT balmunita unravelingthespectrumofkitmutationsingastrointestinalstromaltumorsanindiantertiarycancercenterexperience AT shettyomshree unravelingthespectrumofkitmutationsingastrointestinalstromaltumorsanindiantertiarycancercenterexperience AT guravmamta unravelingthespectrumofkitmutationsingastrointestinalstromaltumorsanindiantertiarycancercenterexperience AT ostwalvikas unravelingthespectrumofkitmutationsingastrointestinalstromaltumorsanindiantertiarycancercenterexperience AT ramaswamyanant unravelingthespectrumofkitmutationsingastrointestinalstromaltumorsanindiantertiarycancercenterexperience AT ramadwarmukta unravelingthespectrumofkitmutationsingastrointestinalstromaltumorsanindiantertiarycancercenterexperience AT desaisangeeta unravelingthespectrumofkitmutationsingastrointestinalstromaltumorsanindiantertiarycancercenterexperience |