PMID- 21154748
OWN - NLM
STAT- MEDLINE
DCOM- 20120913
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 129
IP  - 8
DP  - 2011 Oct 15
TI  - Frequent genomic loss at chr16p13.2 is associated with poor prognosis in 
      colorectal cancer.
PG  - 1848-58
LID - 10.1002/ijc.25841 [doi]
AB  - Genomic alterations play important roles in colorectal cancer (CRC) 
      carcinogenesis. Here, we aimed to identify and characterize recurrent copy-number 
      alterations (CNAs) associated with clinical outcome of CRC by the use of single 
      nucleotide polymorphism arrays, genomic quantitative PCR (qPCR) and fluorescence 
      in situ hybridization (FISH). Colorectal neoplasia specimens and paired germline 
      samples from 144 patients (40 adenomas and 104 carcinomas) as well as 40 CRC cell 
      lines were investigated. This large dataset revealed frequent loss, including 
      homozygous loss, at chr16p13.2 (from 5.9 to 7.42Mb). The loss was observed in 30% 
      of adenomas and even more frequently in carcinomas, 56%, indicating that the loss 
      define a subset of adenomas with a propensity for invasion. Consistent with this, 
      the loss occurred twice as frequent in villous (40%) as in tubular adenomas 
      (20%). The loss occurred independently of microsatellite stability and could be 
      validated by qPCR in an independent sample cohort (n = 71). In Stage II/III, 
      microsatellite stable (MSS) CRC it was associated with poor recurrence free 
      survival (hazard ratio 2.4; p = 0.02; Multivariate Cox regression analysis). No 
      transcriptional consequences of the losses were observed, and the only gene, 
      A2BP1, located in the region showed no mutations. Correlation with other CNAs was 
      established for chr3p22 in carcinomas and chr20p (inverse) in adenomas. FISH 
      documented the chr16p13.2 region to be involved in complex structural 
      rearrangements that included translocation to chr3p22 in some cases. The findings 
      indicate that structural rearrangements involving chr16p13.2 are very frequent in 
      colorectal neoplasia, often lead to homozygous deletion, and are associated with 
      poor clinical outcome.
CI  - Copyright (c) 2011 UICC.
FAU - Andersen, Claus Lindbjerg
AU  - Andersen CL
AD  - Department of Molecular Medicine (MOMA), Aarhus University Hospital, Skejby, 
      Aarhus N, Denmark. cla@ki.au.dk
FAU - Lamy, Philippe
AU  - Lamy P
FAU - Thorsen, Kasper
AU  - Thorsen K
FAU - Kjeldsen, Eigil
AU  - Kjeldsen E
FAU - Wikman, Friedrik
AU  - Wikman F
FAU - Villesen, Palle
AU  - Villesen P
FAU - Oster, Bodil
AU  - Oster B
FAU - Laurberg, Soren
AU  - Laurberg S
FAU - Orntoft, Torben Falck
AU  - Orntoft TF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110311
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
SB  - IM
MH  - Adenoma/*genetics
MH  - Aged
MH  - *Carcinoma/genetics
MH  - Cell Line, Tumor
MH  - *Chromosomes, Human, Pair 16
MH  - Colorectal Neoplasms/*genetics
MH  - *DNA Copy Number Variations
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Male
MH  - Oligonucleotide Array Sequence Analysis
MH  - Polymorphism, Single Nucleotide
MH  - Prognosis
EDAT- 2010/12/15 06:00
MHDA- 2012/09/14 06:00
CRDT- 2010/12/15 06:00
PHST- 2010/08/25 00:00 [received]
PHST- 2010/11/19 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2012/09/14 06:00 [medline]
AID - 10.1002/ijc.25841 [doi]
PST - ppublish
SO  - Int J Cancer. 2011 Oct 15;129(8):1848-58. doi: 10.1002/ijc.25841. Epub 2011 Mar 
      11.