South Asian Journal of Cancer

ORIGINAL ARTICLE: GI CANCER
Year
: 2017  |  Volume : 6  |  Issue : 3  |  Page : 113--117

Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience


Trupti Pai1, Munita Bal2, Omshree Shetty1, Mamta Gurav1, Vikas Ostwal3, Anant Ramaswamy3, Mukta Ramadwar2, Sangeeta Desai4 
1 Division of Molecular Pathology, Tata Memorial Centre, Mumbai, Maharashtra, India
2 Department of Pathology, Tata Memorial Centre, Mumbai, Maharashtra, India
3 Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
4 Division of Molecular Pathology; Department of Pathology, Tata Memorial Centre, Mumbai, Maharashtra, India

Correspondence Address:
Omshree Shetty
Division of Molecular Pathology, Tata Memorial Centre, Mumbai, Maharashtra
India

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.


How to cite this article:
Pai T, Bal M, Shetty O, Gurav M, Ostwal V, Ramaswamy A, Ramadwar M, Desai S. Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience.South Asian J Cancer 2017;6:113-117


How to cite this URL:
Pai T, Bal M, Shetty O, Gurav M, Ostwal V, Ramaswamy A, Ramadwar M, Desai S. Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience. South Asian J Cancer [serial online] 2017 [cited 2020 Mar 28 ];6:113-117
Available from: http://journal.sajc.org/article.asp?issn=2278-330X;year=2017;volume=6;issue=3;spage=113;epage=117;aulast=Pai;type=0