Document Detail


Mutational analysis and clinical correlation of metastatic colorectal cancer.
MedLine Citation:
PMID:  24500602     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes.
METHODS: Under Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for >150 mutations across 15 commonly mutated cancer genes. The chi-square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival.
RESULTS: Broad-based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with rectal cancer versus colon cancer (12.5% vs 0.6%; P < .001) and with age ≥56 years (7% vs 0.9%; P = .02). Conversely, v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations were associated with colon cancer (13% vs 3%; P = .024) and older age (15.8% vs 4.6%; P = .006). TP53 mutations were associated with rectal cancer (30% vs 18%; P = .048), younger age (14% vs 28.7%; P = .007), and men (26.4% vs 14%; P = .03). Lung metastases were associated with PIK3CA mutations (23% vs 8.7%; P = .004). Only mutations in BRAF were independently associated with decreased overall survival (hazard ratio, 2.4; 95% confidence interval, 1.09-5.27; P = .029).
CONCLUSIONS: The current study suggests that underlying molecular profiles can differ between colon and rectal cancers. Further investigation is warranted to assess whether the differences identified are important in determining the optimal treatment course for these patients.
Authors:
Andrea L Russo; Darrell R Borger; Jackie Szymonifka; David P Ryan; Jennifer Y Wo; Lawrence S Blaszkowsky; Eunice L Kwak; Jill N Allen; Raymond C Wadlow; Andrew X Zhu; Janet E Murphy; Jason E Faris; Dora Dias-Santagata; Kevin M Haigis; Leif W Ellisen; Anthony J Iafrate; Theodore S Hong
Publication Detail:
Type:  Journal Article     Date:  2014-02-05
Journal Detail:
Title:  Cancer     Volume:  120     ISSN:  1097-0142     ISO Abbreviation:  Cancer     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-05-07     Completed Date:  2014-06-16     Revised Date:  2014-11-09    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1482-90     Citation Subset:  AIM; IM    
Copyright Information:
© 2014 American Cancer Society.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / chemistry,  genetics*,  mortality,  secondary
Adenomatous Polyposis Coli Protein / genetics
Adult
Aged
Aged, 80 and over
Colonic Neoplasms / chemistry,  genetics*,  mortality,  pathology
DNA Mutational Analysis*
Female
GTP Phosphohydrolases / genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genotype
Humans
Kaplan-Meier Estimate
Male
Membrane Proteins / genetics
Middle Aged
Mutation*
Neoplasm Staging
Phosphatidylinositol 3-Kinases / genetics
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins B-raf / analysis,  genetics*
Rectal Neoplasms / chemistry,  genetics*,  mortality,  pathology
Retrospective Studies
Risk Factors
Tumor Markers, Biological / analysis,  genetics*
Tumor Suppressor Protein p53 / genetics
ras Proteins / genetics
Grant Support
ID/Acronym/Agency:
P50 CA127003/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/APC protein, human; 0/Adenomatous Polyposis Coli Protein; 0/KRAS protein, human; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/TP53 protein, human; 0/Tumor Markers, Biological; 0/Tumor Suppressor Protein p53; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.137/PIK3CA protein, human; EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf; EC 3.6.1.-/GTP Phosphohydrolases; EC 3.6.1.-/NRAS protein, human; EC 3.6.5.2/ras Proteins

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