Cited by 187Colorectal Cancer Treatments and StudiesColorectal Cancer Surgical TreatmentsGenetic factors in colorectal cancer

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RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer

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Yaeger, Rona, Cowell, Elizabeth, Chou, Joanne F., Gewirtz, Alexandra N., Borsu, Laetitia, Vakiani, Efsevia, Solit, David B., Rosen, Neal, Capanu, Marinela, Ladanyi, Marc, Kemeny, Nancy·2015·Cancer

DOI 10.1002/cncr.29196PMC PMC4523078

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Abstract

BACKGROUND: RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. METHODS: We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site‐specific metastasis. RESULTS: Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P < .01). RAS mutant mCRC exhibited a significantly higher cumulative incidence of lung, bone, and brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site‐specific pattern of metastatic spread. CONCLUSIONS: The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site‐specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. Cancer 2015;121:1195–1203. © 2014 American Cancer Society.

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Authors: Yaeger, R., Cowell, E., Chou, J. F., Gewirtz, A. N., Borsu, L., Vakiani, E., Solit, D. B., Rosen, N., Capanu, M., Ladanyi, M., & Kemeny, N.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Corresponding author: Kemeny, Nancy
ORCID: Yaeger, Rona
Chou, Joanne F.
Gewirtz, Alexandra N.
Borsu, Laetitia
Vakiani, Efsevia
Solit, David B.
Rosen, Neal
Capanu, Marinela
Ladanyi, Marc
Kemeny, Nancy
Venue: Cancer
Publisher: Wiley
Published: 2014-12-09
Volume: 121
Issue: 8
Pages: 1195-1203
ISSN: 0008-543X (ISSN-L)
1097-0142
DOI: 10.1002/cncr.29196
PMC: PMC4523078
OpenAlex: W1492286179
Cited by: 187
References: 30
Citations by year: 2026: 7 · 2025: 16 · 2024: 15 · 2023: 9 · 2022: 20 · 2021: 20 · 2020: 19 · 2019: 22 · 2018: 17 · 2017: 21 · 2016: 11 · 2015: 10
FWCI: 6.76
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Cancer (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (P30CA008748, R25CA020449)
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: RAS mutations, PIK3CA mutation, metastatic colorectal cancer, brain metastases, lung metastasis, bone metastasis, liver metastasis, overall survival, KRAS, NRAS, metastatic potential
MeSH terms: Adult, Aged, Aged, 80 and over, Bone Neoplasms, Brain Neoplasms, Female, Humans, Liver Neoplasms, Male, Membrane Proteins, Middle Aged, Mutation, Prognosis, Proto-Oncogene Proteins, Colorectal Neoplasms, Survival Analysis, Proto-Oncogene Proteins p21(ras), ras Proteins, Phosphatidylinositol 3-Kinases, GTP Phosphohydrolases, Young Adult, Class I Phosphatidylinositol 3-Kinases

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RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer

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