A1 Journal article (refereed)
Atypical (non-V600E) BRAF mutations in metastatic colorectal cancer in population and real-world cohorts (2024)

Osterlund, E., Ristimäki, A., Mäkinen, M. J., Kytölä, S., Kononen, J., Pfeiffer, P., Soveri, L., Keinänen, M., Sorbye, H., Nunes, L., Salminen, T., Nieminen, L., Uutela, A., Halonen, P., Ålgars, A., Sundström, J., Kallio, R., Ristamäki, R., Lamminmäki, A., . . . Osterlund, P. (2024). Atypical (non-V600E) BRAF mutations in metastatic colorectal cancer in population and real-world cohorts. International Journal of Cancer, 154(3), 488-503. https://doi.org/10.1002/ijc.34733

JYU authors or editors

Publication details

All authors or editors: Osterlund, Emerik; Ristimäki, Ari; Mäkinen, Markus J.; Kytölä, Soili; Kononen, Juha; Pfeiffer, Per; Soveri, Leena‐Maija; Keinänen, Mauri; Sorbye, Halfdan; Nunes, Luís; et al.

Journal or series: International Journal of Cancer

ISSN: 0020-7136

eISSN: 1097-0215

Publication year: 2024

Publication date: 19/09/2023

Volume: 154

Issue number: 3

Pages range: 488-503

Publisher: John Wiley & Sons

Publication country: United States

Publication language: English

DOI: https://doi.org/10.1002/ijc.34733

Publication open access: Openly available

Publication channel open access: Partially open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/89220

Additional information: This work has been presented in part at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer, held online, July 1 to 4, 2020.

Abstract

BRAF-V600E mutation (mt) is a strong negative prognostic and predictive biomarker in metastatic colorectal cancer (mCRC). Non-V600Emt, designated atypical BRAFmt (aBRAFmt) are rare, and little is known about their frequency, co-mutations and prognostic and predictive role. These were compared between mutational groups of mCRC patients collected from three Nordic population-based or real-world cohorts. Pathology of aBRAFmt was studied. The study included 1449 mCRC patients with 51 (3%) aBRAFmt, 182 (13%) BRAF-V600Emt, 456 (31%) RAS&BRAF wild-type (wt) and 760 (52%) RASmt tumours. aBRAFmt were seen in 2% of real-world and 4% of population-based cohorts. Twenty-six different aBRAFmt were detected, 11 (22%) class 2 (serrated adenocarcinoma in 2/9 tested), 32 (64%) class 3 (serrated in 15/25) and 4 (8%) unclassified. aBRAFmt patients were predominantly male, had more rectal primaries, less peritoneal metastases, deficient mismatch repair in one (2%), and better survival after metastasectomy (89% 5-year overall survival [OS]-rate) compared with BRAF-V600Emt. aBRAFmt and BRAF-V600Emt had poorer performance status and received fewer treatment lines than RAS&BRAFwt and RASmt. OS among aBRAFmt (median 14.4 months) was longer than for BRAF-V600Emt (11.2 months), but shorter than for RAS&BRAFwt (30.5 months) and RASmt (23.4 months). Addition of bevacizumab trended for better OS for the aBRAFmt. Nine patients with aBRAFmt received cetuximab/panitumumab without response. aBRAFmt represents a distinct subgroup differing from other RAS/BRAF groups, with serrated adenocarcinoma in only half. OS for patients with aBRAFmt tumours was slightly better than for BRAF-V600Emt, but worse than for RASmt and RAS&BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.

Keywords: cancer of the large intestine; metastases; biomarkers; oncogenes; mutations; population research; cohort study

Free keywords: aBRAF; BRAFmutation; colorectal cancer; metastatic; non-V600E

Contributing organizations

Ministry reporting: Yes

VIRTA submission year: 2023

Preliminary JUFO rating: 2