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RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer
Open accessAbstract
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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“although RAS mutations have been associated with increased tendency for lung involvement in colorectal cancer (33–35).”
From Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRAS G12C-Mutated Metastatic Colorectal Cancer (2024) · cites this paper as [35]
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Self-citationComparative Genomic Analysis of Primary Versus Metastatic Colorectal Carcinomas
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Metadata
- 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
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2014-12-09
- Volume
- 121
- Issue
- 8
- Pages
- 1195-1203
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- 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
- 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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