KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts

Emerik Osterlund; Ari Ristimäki; Luís Nunes; Soili Kytölä; Sonja Aho; Eetu Heervä; Aki Uutela; Kaisa Lehtomäki; Hanna Stedt; Päivi Halonen; Joel Kontiainen; Timo Muhonen; Raija Kallio; Jari Sundström; Annika Ålgars; Raija Ristamäki; Lasse Nieminen; Halfdan Sorbye; Per Pfeiffer; Tapio Salminen; Arno Nordin; Annamarja Lamminmäki; Markus J Mäkinen; Tobias Sjöblom; Helena Isoniemi; Bengt Glimelius; Pia Osterlund

doi:10.1038/s44276-025-00188-5

KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts

Emerik Osterlund
, Ari Ristimäki
, Luís Nunes
, Soili Kytölä
, Sonja Aho
, Eetu Heervä
, Aki Uutela
, Kaisa Lehtomäki
, Hanna Stedt
, Päivi Halonen
, Joel Kontiainen
, Timo Muhonen
, Raija Kallio
, Jari Sundström
, Annika Ålgars
, Raija Ristamäki
, Lasse Nieminen
, Halfdan Sorbye
, Per Pfeiffer
, Tapio Salminen

Arno Nordin, Annamarja Lamminmäki, Markus J Mäkinen, Tobias Sjöblom, Helena Isoniemi, Bengt Glimelius, Pia Osterlund

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Abstract

BACKGROUND: KRAS and NRAS mutations (mt) are drivers in metastatic colorectal cancer (mCRC). We studied frequencies, characteristics, treatments, and outcomes of different KRASmt and NRASmt in population-based and real-world settings.

METHODS: Three Nordic cohorts were combined and molecularly characterised for KRAS, NRAS, and BRAF-V600E hotspot mutations.

RESULTS: Of 2649 mCRC patients, 2118 were molecularly classified. KRASmt were seen in 49%, NRASmt in 4%, RAS&BRAFwt in 33%, and BRAF-V600Emt in 14%. No differences in clinical characteristics were observed between KRASmt and NRASmt. Median overall survival (OS) was longest among RAS&BRAFwt, intermediate among KRASmt and NRASmt, and shortest among BRAF-V600Emt (28.3 vs 21.4 vs 26.3 vs 9.2 months, respectively). Among the eight most common KRASmt, the only clinical difference was that KRAS-G12S had more distant lymph node metastases (38% vs 18-27%, p = 0.041). KRAS-G12S had shorter OS than KRAS-G12V, KRAS-G12C, KRAS-G12A, and KRAS-G13D. The differences were smaller in treatment groups but withstood in multivariable models. The three most common NRASmt did not differ clinically.

CONCLUSION: KRASmt and NRASmt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.

Original language	English
Article number	72
Journal	BJC reports
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s44276-025-00188-5
Publication status	Published - 21 Oct 2025
Publication type	A1 Journal article-refereed

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SDG 3 Good Health and Well-being

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KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohortsFinal published version, 853 KBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202601211680Licence: CC BY

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Osterlund, E., Ristimäki, A., Nunes, L., Kytölä, S., Aho, S., Heervä, E., Uutela, A., Lehtomäki, K., Stedt, H., Halonen, P., Kontiainen, J., Muhonen, T., Kallio, R., Sundström, J., Ålgars, A., Ristamäki, R., Nieminen, L., Sorbye, H., Pfeiffer, P., ... Osterlund, P. (2025). KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts. BJC reports, 3(1), Article 72. https://doi.org/10.1038/s44276-025-00188-5

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title = "KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts",

abstract = "BACKGROUND: KRAS and NRAS mutations (mt) are drivers in metastatic colorectal cancer (mCRC). We studied frequencies, characteristics, treatments, and outcomes of different KRASmt and NRASmt in population-based and real-world settings.METHODS: Three Nordic cohorts were combined and molecularly characterised for KRAS, NRAS, and BRAF-V600E hotspot mutations.RESULTS: Of 2649 mCRC patients, 2118 were molecularly classified. KRASmt were seen in 49\%, NRASmt in 4\%, RAS\&BRAFwt in 33\%, and BRAF-V600Emt in 14\%. No differences in clinical characteristics were observed between KRASmt and NRASmt. Median overall survival (OS) was longest among RAS\&BRAFwt, intermediate among KRASmt and NRASmt, and shortest among BRAF-V600Emt (28.3 vs 21.4 vs 26.3 vs 9.2 months, respectively). Among the eight most common KRASmt, the only clinical difference was that KRAS-G12S had more distant lymph node metastases (38\% vs 18-27\%, p = 0.041). KRAS-G12S had shorter OS than KRAS-G12V, KRAS-G12C, KRAS-G12A, and KRAS-G13D. The differences were smaller in treatment groups but withstood in multivariable models. The three most common NRASmt did not differ clinically.CONCLUSION: KRASmt and NRASmt are seen in 49\% and 4\% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.",

author = "Emerik Osterlund and Ari Ristim{\"a}ki and Lu{\'i}s Nunes and Soili Kyt{\"o}l{\"a} and Sonja Aho and Eetu Heerv{\"a} and Aki Uutela and Kaisa Lehtom{\"a}ki and Hanna Stedt and P{\"a}ivi Halonen and Joel Kontiainen and Timo Muhonen and Raija Kallio and Jari Sundstr{\"o}m and Annika {\AA}lgars and Raija Ristam{\"a}ki and Lasse Nieminen and Halfdan Sorbye and Per Pfeiffer and Tapio Salminen and Arno Nordin and Annamarja Lamminm{\"a}ki and M{\"a}kinen, \{Markus J\} and Tobias Sj{\"o}blom and Helena Isoniemi and Bengt Glimelius and Pia Osterlund",

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year = "2025",

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day = "21",

doi = "10.1038/s44276-025-00188-5",

language = "English",

volume = "3",

journal = "BJC reports",

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number = "1",

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Osterlund, E, Ristimäki, A, Nunes, L, Kytölä, S, Aho, S, Heervä, E, Uutela, A, Lehtomäki, K, Stedt, H, Halonen, P, Kontiainen, J, Muhonen, T, Kallio, R, Sundström, J, Ålgars, A, Ristamäki, R, Nieminen, L, Sorbye, H, Pfeiffer, P, Salminen, T, Nordin, A, Lamminmäki, A, Mäkinen, MJ, Sjöblom, T, Isoniemi, H, Glimelius, B & Osterlund, P 2025, 'KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts', BJC reports, vol. 3, no. 1, 72. https://doi.org/10.1038/s44276-025-00188-5

TY - JOUR

T1 - KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts

AU - Osterlund, Emerik

AU - Ristimäki, Ari

AU - Nunes, Luís

AU - Kytölä, Soili

AU - Aho, Sonja

AU - Heervä, Eetu

AU - Uutela, Aki

AU - Lehtomäki, Kaisa

AU - Stedt, Hanna

AU - Halonen, Päivi

AU - Kontiainen, Joel

AU - Muhonen, Timo

AU - Kallio, Raija

AU - Sundström, Jari

AU - Ålgars, Annika

AU - Ristamäki, Raija

AU - Nieminen, Lasse

AU - Sorbye, Halfdan

AU - Pfeiffer, Per

AU - Salminen, Tapio

AU - Nordin, Arno

AU - Lamminmäki, Annamarja

AU - Mäkinen, Markus J

AU - Sjöblom, Tobias

AU - Isoniemi, Helena

AU - Glimelius, Bengt

AU - Osterlund, Pia

PY - 2025/10/21

Y1 - 2025/10/21

N2 - BACKGROUND: KRAS and NRAS mutations (mt) are drivers in metastatic colorectal cancer (mCRC). We studied frequencies, characteristics, treatments, and outcomes of different KRASmt and NRASmt in population-based and real-world settings.METHODS: Three Nordic cohorts were combined and molecularly characterised for KRAS, NRAS, and BRAF-V600E hotspot mutations.RESULTS: Of 2649 mCRC patients, 2118 were molecularly classified. KRASmt were seen in 49%, NRASmt in 4%, RAS&BRAFwt in 33%, and BRAF-V600Emt in 14%. No differences in clinical characteristics were observed between KRASmt and NRASmt. Median overall survival (OS) was longest among RAS&BRAFwt, intermediate among KRASmt and NRASmt, and shortest among BRAF-V600Emt (28.3 vs 21.4 vs 26.3 vs 9.2 months, respectively). Among the eight most common KRASmt, the only clinical difference was that KRAS-G12S had more distant lymph node metastases (38% vs 18-27%, p = 0.041). KRAS-G12S had shorter OS than KRAS-G12V, KRAS-G12C, KRAS-G12A, and KRAS-G13D. The differences were smaller in treatment groups but withstood in multivariable models. The three most common NRASmt did not differ clinically.CONCLUSION: KRASmt and NRASmt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.

AB - BACKGROUND: KRAS and NRAS mutations (mt) are drivers in metastatic colorectal cancer (mCRC). We studied frequencies, characteristics, treatments, and outcomes of different KRASmt and NRASmt in population-based and real-world settings.METHODS: Three Nordic cohorts were combined and molecularly characterised for KRAS, NRAS, and BRAF-V600E hotspot mutations.RESULTS: Of 2649 mCRC patients, 2118 were molecularly classified. KRASmt were seen in 49%, NRASmt in 4%, RAS&BRAFwt in 33%, and BRAF-V600Emt in 14%. No differences in clinical characteristics were observed between KRASmt and NRASmt. Median overall survival (OS) was longest among RAS&BRAFwt, intermediate among KRASmt and NRASmt, and shortest among BRAF-V600Emt (28.3 vs 21.4 vs 26.3 vs 9.2 months, respectively). Among the eight most common KRASmt, the only clinical difference was that KRAS-G12S had more distant lymph node metastases (38% vs 18-27%, p = 0.041). KRAS-G12S had shorter OS than KRAS-G12V, KRAS-G12C, KRAS-G12A, and KRAS-G13D. The differences were smaller in treatment groups but withstood in multivariable models. The three most common NRASmt did not differ clinically.CONCLUSION: KRASmt and NRASmt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.

U2 - 10.1038/s44276-025-00188-5

DO - 10.1038/s44276-025-00188-5

M3 - Article

C2 - 41120702

SN - 2731-9377

VL - 3

JO - BJC reports

JF - BJC reports

IS - 1

M1 - 72

ER -

KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts

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