A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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-tekijät tai -toimittajat

Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Osterlund, Emerik; Ristimäki, Ari; Mäkinen, Markus J.; Kytölä, Soili; Kononen, Juha; Pfeiffer, Per; Soveri, Leena‐Maija; Keinänen, Mauri; Sorbye, Halfdan; Nunes, Luís; et al.

Lehti tai sarja: International Journal of Cancer

ISSN: 0020-7136

eISSN: 1097-0215

Julkaisuvuosi: 2024

Ilmestymispäivä: 19.09.2023

Volyymi: 154

Lehden numero: 3

Artikkelin sivunumerot: 488-503

Kustantaja: John Wiley & Sons

Julkaisumaa: Yhdysvallat (USA)

Julkaisun kieli: englanti

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

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisukanavan avoin saatavuus: Osittain avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/89220

Lisätietoja: 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.

Tiivistelmä

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.

YSO-asiasanat: paksusuolisyöpä; etäpesäkkeet; biomarkkerit; syöpägeenit; mutaatiot; väestötutkimus; kohorttitutkimus

Vapaat asiasanat: aBRAF; BRAFmutation; colorectal cancer; metastatic; non-V600E

Liittyvät organisaatiot

OKM-raportointi: Kyllä

VIRTA-lähetysvuosi: 2023

Alustava JUFO-taso: 2