RRC ID 68809
著者 Fujino T, Suda K, Sakai K, Murakami I, Shimizu S, Ohara S, Koga T, Hamada A, Soh J, Nishio K, Mitsudomi T.
タイトル Intra-tumor and Inter-tumor Heterogeneity in MET Exon 14 Skipping Mutations and Co-mutations in Pulmonary Pleomorphic Carcinomas.
ジャーナル Clin Lung Cancer
Abstract BACKGROUND:MET exon 14 skipping mutation is a driver mutation in lung cancer and is highly enriched in pulmonary pleomorphic carcinomas (PPCs). Whether there is intratumor or intertumor heterogeneity in MET exon 14 skipping status or in co-occurring genetic alterations in lung cancers driven by MET exon 14 skipping is unknown.
METHODS:We analyzed tumor specimens obtained from 23 PPC patients (10 autopsied and 13 surgically resected). MET exon 14 skipping was detected by RT-PCR. For patients with MET exon 14 skipping mutation, further analyses were performed. Genomic DNA (gDNA) was extracted from various histological components for each patient who underwent surgical resection (to assess intratumor heterogeneity). In autopsied patients, gDNA and total RNA were extracted from all metastatic lesions (to assess intertumor heterogeneity).
RESULTS:MET exon 14 skipping mutation was detected in 4 patients (4/23, 17.4%): two surgically resected and two autopsied patients. We found no intratumor or intertumor heterogeneity in MET exon 14 skipping mutation status in these patients. We observed intratumor and intertumor heterogeneity in the copy number variations and/or mutational status of cancer-related genes; some of these differences may have an impact on MET tyrosine kinase inhibitor (TKI) efficacy.
CONCLUSION:In our exploratory analysis of four cases, we observed that MET exon 14 skipping mutations are distributed homogeneously throughout histological components and between metastatic lesions. Our results also suggest that there is marked intertumor and intratumor heterogeneity in co-occurring genetic alterations, and therapeutic implications of such heterogeneity should be evaluated in future studies.
巻・号 23(3)
ページ e185-e195
公開日 2022-5-1
DOI 10.1016/j.cllc.2021.09.005
PII S1525-7304(21)00246-1
PMID 34702670
MeSH Carcinoma* DNA Copy Number Variations Exons / genetics Humans Lung Neoplasms* / pathology Mutation / genetics Proto-Oncogene Proteins c-met / genetics*
リソース情報
ヒト・動物細胞 Ba/F3-CL1(RCB4474)