PMID- 11979555
OWN - NLM
STAT- MEDLINE
DCOM- 20020723
LR  - 20161124
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 34
IP  - 2
DP  - 2002 Jun
TI  - Detailed genomic mapping and expression analyses of 12p amplifications in 
      pancreatic carcinomas reveal a 3.5-Mb target region for amplification.
PG  - 211-23
AB  - Previous cytogenetic and comparative genomic hybridization (CGH) analyses have 
      shown that the gain of chromosome arm 12p is frequent in pancreatic carcinomas. 
      We investigated 15 pancreatic carcinoma cell lines using CGH, fluorescence in 
      situ hybridization (FISH), and semiquantitative polymerase chain reaction (PCR) 
      to characterize 12p amplifications in detail. The CGH analysis revealed gains of 
      12p in four of the cell lines and local amplification within 12p11-12 in six cell 
      lines. By FISH analysis, using precisely mapped YAC clones, the commonly 
      amplified region was found to be approximately 5 Mb. The amplified segment 
      extended from YAC 753f12, covering the KRAS2 locus, to YAC 891f1, close to the 
      centromere. A semiquantitative PCR methodology was used to estimate genomic copy 
      numbers of 14 precisely mapped expressed sequence tags (ESTs) and sequence-tagged 
      sites, located within this interval. The level of amplification ranged from two- 
      to 12-fold. The produced gene copy profiles revealed a 3.5-Mb segment with 
      various local amplifications. This region includes KRAS2 and ranges from D12S1617 
      to sts-N38796. Two of the cell lines (primary and metastatic tumor from the same 
      patient) showed amplification peaks within the distal region of this segment, two 
      had peaks within the proximal region, one showed subpeaks in both regions, and 
      one displayed amplification of the entire region. Chromosome segment-specific 
      cDNA array analysis of 29 expressed sequences within the whole interval between 
      D12S1617 and sts-N38796 indicated overexpression of four ESTs, two corresponding 
      to DEC2 and PPFIBP1, and two to ESTs with unknown function. Expression analysis 
      of these and of KRAS2 showed specific overexpression in the six cell lines with 
      local 12p amplifications. These findings indicate two target regions within the 
      3.5-Mb segment in 12p11-12, one proximal including PPFIBP1, and one distal 
      including KRAS2.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Heidenblad, Markus
AU  - Heidenblad M
AD  - Department of Clinical Genetics, Lund University Hospital, Sweden. 
      markus.heidenblad@klingen.lu.se
FAU - Jonson, Tord
AU  - Jonson T
FAU - Mahlamaki, Eija H
AU  - Mahlamaki EH
FAU - Gorunova, Ludmila
AU  - Gorunova L
FAU - Karhu, Ritva
AU  - Karhu R
FAU - Johansson, Bertil
AU  - Johansson B
FAU - Hoglund, Mattias
AU  - Hoglund M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (DNA, Neoplasm)
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  - Carcinoma/*genetics
MH  - Chromosome Mapping/*methods
MH  - Chromosomes, Human, Pair 12/*genetics
MH  - DNA Mutational Analysis/methods
MH  - DNA, Neoplasm/genetics
MH  - Gene Amplification/*genetics
MH  - Gene Expression Profiling/*methods
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Genes, Neoplasm/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Nucleic Acid Hybridization
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Pancreatic Neoplasms/*genetics
MH  - Proto-Oncogene Proteins/biosynthesis/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Tumor Cells, Cultured
MH  - ras Proteins
EDAT- 2002/04/30 10:00
MHDA- 2002/07/24 10:01
CRDT- 2002/04/30 10:00
PHST- 2002/04/30 10:00 [pubmed]
PHST- 2002/07/24 10:01 [medline]
PHST- 2002/04/30 10:00 [entrez]
AID - 10.1002/gcc.10063 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2002 Jun;34(2):211-23. doi: 10.1002/gcc.10063.