1. Significance of RAS mutations in pulmonary metastases of patients with colorectal cancer
- Author
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Hiroomi Ogawa, Yoichi Ohtaki, Yoko Motegi, Takahiro Ohkawa, Ryuji Katoh, Takehiko Yokobori, Tatsuo Ichihara, Kengo Usui, Kimihiro Shimizu, Sumihito Nobusawa, Toshiki Yajima, Ken Shirabe, Hideaki Yokoo, Akira Mogi, Yasumasa Mitani, Norifumi Harimoto, Kai Obayashi, Seshiru Nakazawa, and Takamichi Igarashi
- Subjects
Male ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Lung Neoplasms ,Colorectal cancer ,medicine.disease_cause ,GTP Phosphohydrolases ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,medicine ,Humans ,neoplasms ,Genotyping ,Aged ,Aged, 80 and over ,Mutation ,business.industry ,High-Throughput Nucleotide Sequencing ,Membrane Proteins ,Cancer ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Surgery ,KRAS ,Colorectal Neoplasms ,business ,Carcinogenesis - Abstract
RAS/BRAF mutations of colorectal cancer (CRC) play a crucial role in carcinogenesis and cancer progression and need to be considered for the therapeutic strategy choice. We used next-generation-sequencing (NGS) technology to assess RAS/BRAF mutation differences between primary CRC and corresponding pulmonary metastases (PMs). We examined the mutation statuses of the KRAS 12/13/61/146, NRAS 12/13/61/146, and BRAF 600 codons in genomic DNA from fresh-frozen or formalin-fixed paraffin-embedded tissues derived from 34 primary lesions and 52 corresponding PMs from 36 patients with CRC. We found RAS mutations in 76% (26/34) of primary CRC lesions and in 86% (31/36) of PMs. While 27% (7/26) of the primary CRC RAS mutations were heterogeneous, all the RAS mutations in PMs were homogeneous. Of the mutations in PMs, 71% (22/31) were KRAS G>A transitions, of which 82% (18/22) were KRAS G12D or G13D. The RAS mutation discordance between primary tumors and PMs was 12.1% (4/33). RAS mutations with the same genotyping were detected in all synchronous and metachronous PMs from 9 patients. We found no BRAF mutations in either primary or pulmonary tissues. Our NGS analysis suggests that RAS mutations of PM of patients with CRC are more common than initially thought. The presence of KRAS mutations in CRC specimens, especially G12D or G13D mutations, seems to promote PM formation.
- Published
- 2019