PMID- 21743433
OWN - NLM
STAT- MEDLINE
DCOM- 20120328
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 24
IP  - 12
DP  - 2011 Dec
TI  - KRAS mutant allele-specific imbalance in lung adenocarcinoma.
PG  - 1571-7
LID - 10.1038/modpathol.2011.109 [doi]
AB  - The significance of KRAS mutant allele-specific imbalance (MASI) in lung 
      adenocarcinomas is unknown. KRAS MASI was defined as predominance of the mutant 
      allele over the wild-type allele. We assessed the frequency of KRAS MASI by 
      comparing peak heights of mutant and wild-type alleles on sequencing 
      electropherograms and by KRAS fluorescence in situ hybridization (FISH). A review 
      of sequencing electropherograms of 207 KRAS-mutated lung adenocarcinomas 
      demonstrated 23 (11%) cases with the mutant allele peak higher than the wild-type 
      allele peak and 15 (7%) cases with the mutant allele peak equal to the wild-type 
      allele peak. Of 17 cases with the mutant allele peak higher or equal to the 
      wild-type allele peak, 8 (47%) showed KRAS amplification by FISH. KRAS FISH 
      analysis of 36 KRAS-mutated lung adenocarcinomas with the mutant allele peak 
      lower than the wild-type allele peak, 21 KRAS and EGFR wild-type and 16 
      EGFR-mutated adenocarcinomas showed no KRAS amplification. KRAS MASI was 
      associated with selective amplification of the KRAS mutant allele (P<0.001). 
      Patients with KRAS MASI showed worse overall survival. The cumulative proportion 
      surviving at 17 months for KRAS MASI group was 35% compared with 84.1% for 
      patients with KRAS mutant allele peak lower than wild-type allele peak (P=0.012). 
      The adverse prognostic significance of KRAS MASI was independent of clinical 
      stage and was maintained among stage I patients. The detection of KRAS MASI in 
      lung adenocarcinomas by sequencing electropherograms may identify patients with 
      more aggressive disease.
FAU - Chiosea, Simion I
AU  - Chiosea SI
AD  - Department of Pathology, University of Pittsburgh Medical Center, Presbyterian 
      University Hospital, Pittsburgh, PA, USA. chioseasi@upmc.edu
FAU - Sherer, Carol K
AU  - Sherer CK
FAU - Jelic, Tomislav
AU  - Jelic T
FAU - Dacic, Sanja
AU  - Dacic S
LA  - eng
PT  - Journal Article
DEP - 20110708
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
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  - Adenocarcinoma of Lung
MH  - Aged
MH  - *Allelic Imbalance
MH  - Biomarkers, Tumor/*genetics
MH  - DNA Mutational Analysis
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Gene Amplification
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*genetics/mortality/pathology
MH  - Male
MH  - *Mutation
MH  - Neoplasm Staging
MH  - Phenotype
MH  - Prognosis
MH  - Prospective Studies
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Time Factors
MH  - ras Proteins/*genetics
EDAT- 2011/07/12 06:00
MHDA- 2012/03/29 06:00
CRDT- 2011/07/12 06:00
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2012/03/29 06:00 [medline]
AID - S0893-3952(22)03104-0 [pii]
AID - 10.1038/modpathol.2011.109 [doi]
PST - ppublish
SO  - Mod Pathol. 2011 Dec;24(12):1571-7. doi: 10.1038/modpathol.2011.109. Epub 2011 
      Jul 8.