RAS/RAF mutations and microsatellite instability status in primary colorectal cancers according to HER2 amplification.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Microsatellite Instability* ; Colorectal Neoplasms*/genetics ; Colorectal Neoplasms*/pathology ; Receptor, ErbB-2*/genetics ; Receptor, ErbB-2*/metabolism ; Mutation* ; Gene Amplification*; Humans ; Female ; Male ; Middle Aged ; Aged ; Adult ; Aged, 80 and over ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; High-Throughput Nucleotide Sequencing ; ras Proteins/genetics

HER2 amplification-associated molecular alterations and clinicopathologic features in colorectal cancers (CRCs) have not been well established. In this study, we assessed the prevalence of HER2 amplification and microsatellite instability (MSI) status of 992 patients with primary CRC. In addition, molecular alterations of HER2 amplified and unamplified CRCs were examined and compared by next-generation sequencing. HER2 amplifications were found in 41 (4.1%) of 992 primary CRCs. HER2 amplification was identified in 1.0% of the right colonic tumors, 5.1% of the left colonic tumors, and 4.8% of the rectal tumors. Approximately 95% of HER2 amplification was observed in the left colon and rectum. Seven (87.5%) of eight metastatic tumors showed HER2 amplification. Most clinicopathologic features were unrelated to HER2 amplification except tumor size and MSI status. All 41 HER2 amplified CRCs were microsatellite stable. In a molecular analysis of frequently identified somatic mutations in CRCs, HER2 amplified CRCs showed a lower rate of KRAS mutations (24.4%) but a higher rate of TP53 mutations (83%) than unamplified CRCs. No BRAF and NRAS mutations were identified in HER2 amplified CRCs. Our study suggests that HER2 amplified CRCs are mutually exclusive of MSI and harbor less frequent KRAS/NRAS/BRAF mutations but frequent T53 mutations.
(© 2024. The Author(s).)

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JUNH2021 Jeju National University Hospital

0 (ERBB2 protein, human)
0 (KRAS protein, human)
0 (BRAF protein, human)

Date Created: 20240519 Date Completed: 20240519 Latest Revision: 20240528

20240528

PMC11102903

10.1038/s41598-024-62096-x

38763942