KITgenetic alterations in breast cancer
- 2 November 2022
- journal article
- research article
- Published by BMJ in Journal of Clinical Pathology
- Vol. 77 (1), 40-45
- https://doi.org/10.1136/jcp-2022-208611
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.Keywords
Funding Information
- National Cancer Institute (P30CA008748)
- National Institutes of Health/ National Cancer Institute (P50 CA247749)
- Breast Cancer Research Foundation
- Susan G. Komen
- Cycle for Survival
This publication has 53 references indexed in Scilit:
- Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged SkinJournal of Clinical Oncology, 2013
- Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutationsHistopathology, 2012
- KIT as a Therapeutic Target in Metastatic MelanomaJAMA, 2011
- A Phase II Study of Imatinib Mesylate and Capecitabine in Metastatic Breast Cancer: Southwest Oncology Group Study 0338Clinical Breast Cancer, 2008
- Imatinib mesylate (Gleevec®) in advanced breast cancer-expressing C-Kit or PDGFR-β: clinical activity and biological correlationsAnnals of Oncology, 2008
- c-KIT overexpression, without gene amplification and mutation, in paediatric renal tumoursJournal of Clinical Pathology, 2007
- A phase II trial of imatinib mesylate monotherapy in patients with metastatic breast cancerBreast Cancer Research and Treatment, 2005
- Original Paper.Histopathology, 2002
- Expression of c-kit protein in proliferative lesions of human breast: sexual difference and close association with phosphotyrosine statusZeitschrift für Krebsforschung und Klinische Onkologie, 2002
- pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐upHistopathology, 1991