Synapse - KIT genetic alterations in breast cancer

KIT genetic alterations in breast cancer Journal Article

Authors:	Vahdatinia, M.; Derakhshan, F.; Da Cruz Paula, A.; Dopeso, H.; Marra, A.; Gazzo, A. M.; Brown, D.; Selenica, P.; Ross, D. S.; Razavi, P.; Zhang, H.; Weigelt, B.; Wen, H. Y.; Brogi, E.; Reis-Filho, J. S.; Pareja, F.
Article Title:	KIT genetic alterations in breast cancer
Abstract:	Aims Activating somatic mutations or gene amplification of KIT result in constitutive activation of its receptor tyrosine kinase, which is targetable in various solid tumours. Here, we sought to investigate the presence of KIT genetic alterations in breast cancer (BC) and characterise the histological and genomic features of these tumours. Methods A retrospective analysis of 5,575 BCs previously subjected to targeted sequencing using the FDA-authorised Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay was performed to identify BCs with KIT alterations. A histological assessment of KIT-altered BCs was conducted, and their repertoire of genetic alterations was compared with that of BCs lacking KIT genetic alterations, matched for age, histological type, oestrogen receptor/HER2 status and sample type. Results We identified 18 BCs (0.32%), including 9 primary and 9 metastatic BCs, with oncogenic/likely oncogenic genetic alterations affecting KIT, including activating somatic mutations (n=4) or gene amplification (n=14). All KIT-altered BCs were of high histological grade, although no distinctive histological features were observed. When compared with BCs lacking KIT genetic alterations, no distinctive genetic features were identified. In two metastatic KIT-altered BCs in which the matched primary BC had also been analysed by MSK-IMPACT, the KIT mutations were found to be restricted to the metastatic samples, suggesting that they were late events in the evolution of these cancers. Conclusions KIT genetic alterations are vanishingly rare in BC. KIT-altered BCs are of high grade but lack distinctive histological features. Genetic alterations in KIT might be late events in the evolution and/or progression of BC. © 2024 BMJ Publishing Group. All rights reserved.
Keywords:	retrospective studies; genetics; mutation; proto-oncogene proteins c-kit; breast cancer; gene amplification; breast neoplasms; retrospective study; breast tumor; genomics; humans; human; female
Journal Title:	Journal of Clinical Pathology
Volume:	77
Issue:	1
ISSN:	0021-9746
Publisher:	BMJ Publishing Group Ltd.
Date Published:	2024-01-01
Start Page:	40
End Page:	45
Language:	English
DOI:	10.1136/jcp-2022-208611
PUBMED:	36323507
PROVIDER:	scopus
PMCID:	PMC10151428
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142324563&doi=10.1136%2fjcp-2022-208611&partnerID=40&md5=8a325d91a7ffa90ab5ba8e358adba13b
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding authors are MSK authors: Jorge S Reis-Filho and Fresia Pareja -- Source: Scopus