PMID- 23599154
OWN - NLM
STAT- MEDLINE
DCOM- 20140515
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 26
IP  - 10
DP  - 2013 Oct
TI  - KRAS mutant allele-specific imbalance is associated with worse prognosis in 
      pancreatic cancer and progression to undifferentiated carcinoma of the pancreas.
PG  - 1346-54
LID - 10.1038/modpathol.2013.71 [doi]
AB  - KRAS codon 12 mutations are present in about 90% of ductal adenocarcinomas and in 
      undifferentiated carcinomas of the pancreas. The role of KRAS copy number changes 
      and resulting KRAS mutant allele-specific imbalance (MASI) in ductal 
      adenocarcinoma (n=94), and its progression into undifferentiated carcinoma of the 
      pancreas (n=25) was studied by direct sequencing and KRAS fluorescence in situ 
      hybridization (FISH). Semi-quantitative evaluation of sequencing 
      electropherograms showed KRAS MASI (ie, mutant allele peak higher than or equal 
      to the wild-type allele peak) in 22 (18.4%) cases. KRAS FISH (performed on 45 
      cases) revealed a trend for more frequent KRAS amplification among cases with 
      KRAS MASI (7/20, 35% vs 3/25, 12%, P=0.08). KRAS amplification by FISH was seen 
      only in undifferentiated carcinomas (10/24, 42% vs 0/21 pancreatic ductal 
      adenocarcinoma, 0%, P=0.0007). In 6 of 11 cases with both undifferentiated and 
      well-differentiated components, transition to undifferentiated carcinoma was 
      associated with an increase in KRAS copy number, due to amplification and/or 
      chromosome 12 hyperploidy. Pancreatic carcinomas with KRAS MASI (compared to 
      those without MASI) were predominantly undifferentiated (16/22, 73% vs 9/97, 9%, 
      P<0.001), more likely to present at clinical stage IV (5/22, 23% vs 7/97, 7%, 
      P=0.009), and were associated with shorter overall survival (9 months, 95% 
      confidence interval, 5-13, vs 22 months, 95% confidence interval, 17-27; P=0.015) 
      and shorter disease-free survival (5 months, 95% confidence interval, 2-8 vs 13 
      months, 95% confidence interval, 10-16; P=0.02). Our findings suggest that in a 
      subset of ductal adenocarcinomas, KRAS MASI correlates with the progression to 
      undifferentiated carcinoma of the pancreas.
FAU - Krasinskas, Alyssa M
AU  - Krasinskas AM
AD  - Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, 
      USA.
FAU - Moser, A James
AU  - Moser AJ
FAU - Saka, Burcu
AU  - Saka B
FAU - Adsay, N Volkan
AU  - Adsay NV
FAU - Chiosea, Simion I
AU  - Chiosea SI
LA  - eng
GR  - UL1 RR024153/RR/NCRR NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - UL1TR000005/TR/NCATS NIH HHS/United States
GR  - UL1RR024153/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130419
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 (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  - Aged
MH  - Alleles
MH  - *Allelic Imbalance
MH  - Carcinoma/*genetics/metabolism/pathology
MH  - Carcinoma, Pancreatic Ductal/*genetics/metabolism/pathology
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Pancreatic Neoplasms/*genetics/metabolism/pathology
MH  - Prognosis
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - Proto-Oncogene Proteins p21(ras)
MH  - ras Proteins/*genetics/metabolism
PMC - PMC4128625
MID - NIHMS591158
COIS- Disclosure/conflict of interest The John F Fortney Charitable Pancreatic Cancer 
      Research Group and Mellie's Mission provided financial support. Support for 
      advice regarding regulatory matters was provided by the National Institutes of 
      Health through Grant Numbers UL1RR024153 and UL1TR000005.
EDAT- 2013/04/20 06:00
MHDA- 2014/05/16 06:00
PMCR- 2014/08/11
CRDT- 2013/04/20 06:00
PHST- 2013/01/16 00:00 [received]
PHST- 2013/02/18 00:00 [revised]
PHST- 2013/02/19 00:00 [accepted]
PHST- 2013/04/20 06:00 [entrez]
PHST- 2013/04/20 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
PHST- 2014/08/11 00:00 [pmc-release]
AID - S0893-3952(22)03037-X [pii]
AID - 10.1038/modpathol.2013.71 [doi]
PST - ppublish
SO  - Mod Pathol. 2013 Oct;26(10):1346-54. doi: 10.1038/modpathol.2013.71. Epub 2013 
      Apr 19.