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Atypical (non-V600E) BRAF mutations in metastatic colorectal cancer in population and real-world cohorts

Publiceringsår

2023

Upphovspersoner

Osterlund, Emerik; Ristimäki, Ari; Mäkinen, Markus J.; Kytölä, Soili; Kononen, Juha; Pfeiffer, Per; Soveri, Leena‐Maija; Keinänen, Mauri; Sorbye, Halfdan; Nunes, Luís; Salminen, Tapio; Nieminen, Lasse; Uutela, Aki; Halonen, Päivi; Ålgars, Annika; Sundström, Jari; Kallio, Raija; Ristamäki, Raija; Lamminmäki, Annamarja; Stedt, Hanna; Heervä, Eetu; Kuopio, Teijo; Sjöblom, Tobias; Isoniemi, Helena; Glimelius, Bengt; Osterlund, Pia
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Abstrakt

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.
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Organisationer och upphovspersoner

Åbo universitet

Ristamäki Raija

Sundström Jari

Ålgars Annika

Heervä Eetu

Östra Finlands universitet

Lamminmäki Annamarja

Stedt Hanna Pauliina

Helsingfors universitet

Uutela Aki

Ristimäki Ari

Osterlund Emerik

Isoniemi Helena

Soveri Leena-Maija

Osterlund Pia

Halonen Päivi

Kytölä Soili

Tammerfors universitet

Salminen Tapio

Uleåborgs universitet

Mäkinen Markus

Kallio Raija Sinikka

Helsingforsregionens universitetscentralsjukhus specialupptagningsområde

Uutela Aki

Ristimäki Ari

Osterlund Emerik

Isoniemi Helena

Soveri Leena-Maija

Osterlund Pia

Halonen Päivi

Kytölä Soili

Kuopio universitetssjukhus specialupptagningsområde

Stedt Hanna

Lamminmäki Annamarja

Stedt H

Publikationstyp

Publikationsform

Artikel

Moderpublikationens typ

Tidning

Artikelstyp

En originalartikel

Målgrupp

Vetenskaplig

Kollegialt utvärderad

Kollegialt utvärderad

UKM:s publikationstyp

A1 Originalartikel i en vetenskaplig tidskrift

Publikationskanalens uppgifter

Moderpublikationens namn

International Journal of Cancer

Volym

154

Nummer

3

Sidor

488-503

Publikationsforum

58292

Publikationsforumsnivå

2

Öppen tillgång

Öppen tillgänglighet i förläggarens tjänst

Ja

Öppen tillgång till publikationskanalen

Delvis öppen publikationskanal

Licens för förläggarens version

CC BY NC

Parallellsparad

Ja

Övriga uppgifter

Vetenskapsområden

Biomedicinska vetenskaper; Cancersjukdomar

Nyckelord

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Förlagets internationalitet

Internationell

Språk

engelska

Internationell sampublikation

Ja

Sampublikation med ett företag

Ja

DOI

10.1002/ijc.34733

Publikationen ingår i undervisnings- och kulturministeriets datainsamling

Ja