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CC BY-NC-ND 4.0 · South Asian J Cancer 2017; 06(03): 113-117
DOI: 10.4103/sajc.sajc_275_16
ORIGINAL ARTICLE : GI Cancer

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

Trupti Pai
Division of Molecular Pathology, Tata Memorial Centre, Mumbai, Maharashtra
,
Munita Bal
Department of Pathology, Tata Memorial Centre, Mumbai, Maharashtra
,
Omshree Shetty
Division of Molecular Pathology, Tata Memorial Centre, Mumbai, Maharashtra
,
Mamta Gurav
Division of Molecular Pathology, Tata Memorial Centre, Mumbai, Maharashtra
,
Vikas Ostwal
Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra
,
Anant Ramaswamy
Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra
,
Mukta Ramadwar
Department of Pathology, Tata Memorial Centre, Mumbai, Maharashtra
,
Sangeeta Desai
Division of Molecular Pathology, Tata Memorial Centre, Mumbai, Maharashtra
Department of Pathology, Tata Memorial Centre, Mumbai, Maharashtra
› Author Affiliations Financial support and sponsorship: The support from Molecular Pathology, Surgical Pathology and Medical Oncology GI Unit is acknowledged.
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Abstract

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.

Key words

Exon11 - exon9 - gastrointestinal stromal tumors - KIT - wild type


Publication History

Article published online:
22 December 2020

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