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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We studied frequencies, characteristics, treatments, and outcomes of different KRASmt and NRASmt in population-based and real-world settings.</p><p><strong>Methods: </strong>Three Nordic cohorts were combined and molecularly characterised for KRAS, NRAS, and BRAF-V600E hotspot mutations.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":519964,"journal":{"name":"BJC reports","volume":"3 1","pages":"72"},"PeriodicalIF":0.0000,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts.\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Three Nordic cohorts were combined and molecularly characterised for KRAS, NRAS, and BRAF-V600E hotspot mutations.</p><p><strong>Results: </strong>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. 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引用次数: 0
摘要
背景：KRAS和NRAS突变（mt）是转移性结直肠癌（mCRC）的驱动因素。我们研究了KRASmt和NRASmt在人群和现实世界中的频率、特征、治疗和结果。方法：结合三个北欧队列，对KRAS、NRAS和BRAF-V600E热点突变进行分子表征。结果：在2649例mCRC患者中，有2118例被分子分类。KRASmt占49%，NRASmt占4%，RAS&BRAFwt占33%，BRAF-V600Emt占14%。KRASmt和NRASmt的临床特征无差异。中位总生存期（OS） RAS&BRAFwt组最长，KRASmt和NRASmt组居中，BRAF-V600Emt组最短（分别为28.3个月、21.4个月、26.3个月和9.2个月）。在8种最常见的KRASmt中，唯一的临床差异是KRAS-G12S有更多的远处淋巴结转移（38% vs 18-27%, p = 0.041）。KRAS-G12S的生存期比KRAS-G12V、KRAS-G12C、KRAS-G12A和KRAS-G13D短。治疗组的差异较小，但在多变量模型中存在差异。三种最常见的NRASmt在临床上没有差异。结论：KRASmt和NRASmt分别占mCRC的49%和4%。不同RASmt间无临床相关差异。KRASmt是一种常见的亚组，其结果有望通过新开发的药物得到改善。
KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts.
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.
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