PMID- 22290300
OWN - NLM
STAT- MEDLINE
DCOM- 20121031
LR  - 20161125
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 131
IP  - 8
DP  - 2012 Oct 15
TI  - Mutant allele-specific imbalance modulates prognostic impact of KRAS mutations in 
      colorectal adenocarcinoma and is associated with worse overall survival.
PG  - 1810-7
LID - 10.1002/ijc.27461 [doi]
AB  - The prognostic impact of distinct KRAS mutations in colorectal carcinomas is not 
      fully characterized. We hypothesized that the prognostic impact of KRAS mutations 
      is modulated by KRAS mutant allele-specific imbalance (MASI). KRAS MASI was 
      assessed by sequencing electropherograms in KRAS-mutated colorectal carcinomas (N 
      = 394, prospectively tested). The mechanism of KRAS MASI was studied by 
      fluorescence in situ hybridization (FISH; N = 50). FISH showed that KRAS MASI 
      developed by chromosome 12 hyperploidy (9/18, 50%) or KRAS amplification (1/18, 
      5.5%). KRAS MASI was more common in tumors with KRAS codon 13 than with codon 12 
      mutations [24/81, 30% vs. 54/313, 17%; odds ratio (OR), 2.0, 95% confidence 
      interval (CI), 1.2-3.5; p = 0.01]. KRAS MASI was correlated with overall survival 
      (N = 358, median follow-up = 21 months). In a multivariate analysis, KRAS codon 
      13 MASI was an independent adverse prognostic factor (compared to codon 13 
      mutants without MASI combined with all codon 12 mutants; adjusted hazard ratio, 
      2.2, 95% CI: 1.2-3.9; p = 0.01). KRAS MASI arises through chromosome 12 
      hyperploidy or KRAS amplification and, when affects KRAS codon 13, is associated 
      with worse overall survival.
CI  - Copyright (c) 2012 UICC.
FAU - Hartman, D J
AU  - Hartman DJ
AD  - Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, 
      USA.
FAU - Davison, J M
AU  - Davison JM
FAU - Foxwell, T J
AU  - Foxwell TJ
FAU - Nikiforova, M N
AU  - Nikiforova MN
FAU - Chiosea, S I
AU  - Chiosea SI
LA  - eng
PT  - Journal Article
DEP - 20120322
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Codon)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adenocarcinoma/*genetics/*mortality/pathology
MH  - Alleles
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Codon/genetics
MH  - Colorectal Neoplasms/*genetics/*mortality/pathology
MH  - Exons/genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - *Microsatellite Instability
MH  - Microsatellite Repeats/*genetics
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Prospective Studies
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Survival Rate
MH  - ras Proteins/genetics
EDAT- 2012/02/01 06:00
MHDA- 2012/11/01 06:00
CRDT- 2012/02/01 06:00
PHST- 2011/08/19 00:00 [received]
PHST- 2012/01/14 00:00 [revised]
PHST- 2012/01/18 00:00 [accepted]
PHST- 2012/02/01 06:00 [entrez]
PHST- 2012/02/01 06:00 [pubmed]
PHST- 2012/11/01 06:00 [medline]
AID - 10.1002/ijc.27461 [doi]
PST - ppublish
SO  - Int J Cancer. 2012 Oct 15;131(8):1810-7. doi: 10.1002/ijc.27461. Epub 2012 Mar 
      22.