PMID- 17492757
OWN - NLM
STAT- MEDLINE
DCOM- 20070830
LR  - 20211203
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 46
IP  - 8
DP  - 2007 Aug
TI  - Loss of distal 11q is associated with DNA repair deficiency and reduced 
      sensitivity to ionizing radiation in head and neck squamous cell carcinoma.
PG  - 761-75
AB  - About 45% of head and neck squamous cell carcinomas (HNSCC) are characterized by 
      amplification of chromosomal band 11q13. This amplification occurs by a 
      breakage-fusion-bridge (BFB) cycle mechanism. The first step in the BFB cycle 
      involves breakage and loss of distal 11q, from FRA11F (11q14.2) to 11qter. 
      Consequently, numerous genes, including three critical genes involved in the DNA 
      damage response pathway, MRE11A, ATM, and H2AFX are lost in the step preceding 
      11q13 amplification. We hypothesized that this partial loss of genes on distal 
      11q may lead to a diminished DNA damage response in HNSCC. Characterization of 
      HNSCC using fluorescence in situ hybridization (FISH) revealed concurrent partial 
      loss of MRE11A, ATM, and H2AFX in all four cell lines with 11q13 amplification 
      and in four of seven cell lines without 11q13 amplification. Quantitative 
      microsatellite analysis and loss of heterozygosity studies confirmed the distal 
      11q loss. FISH evaluation of a small series of HNSCC, ovarian, and breast cancers 
      confirmed the presence of 11q loss in at least 60% of these tumors. All cell 
      lines with distal 11q loss exhibited a diminished DNA damage response, as 
      measured by a decrease in the size and number of gamma-H2AX foci and increased 
      chromosomal instability following treatment with ionizing radiation. In 
      conclusion, loss of distal 11q results in a defective DNA damage response in 
      HNSCC. Distal 11q loss was also unexpectedly associated with reduced sensitivity 
      to ionizing radiation. Although the literature attributes the poor prognosis in 
      HNSCC to 11q13 gene amplification, our results suggest that distal 11q deletions 
      may be an equally significant factor.
FAU - Parikh, Rahul A
AU  - Parikh RA
AD  - Department of Human Genetics, University of Pittsburgh Graduate School of Public 
      Health, Pittsburgh, PA 15261, USA.
FAU - White, Jason S
AU  - White JS
FAU - Huang, Xin
AU  - Huang X
FAU - Schoppy, David W
AU  - Schoppy DW
FAU - Baysal, Bora E
AU  - Baysal BE
FAU - Baskaran, Rajasekaran
AU  - Baskaran R
FAU - Bakkenist, Christopher J
AU  - Bakkenist CJ
FAU - Saunders, William S
AU  - Saunders WS
FAU - Hsu, Lih-Ching
AU  - Hsu LC
FAU - Romkes, Marjorie
AU  - Romkes M
FAU - Gollin, Susanne M
AU  - Gollin SM
LA  - eng
GR  - P30CA047904-169019/CA/NCI NIH HHS/United States
GR  - P30CA47904/CA/NCI NIH HHS/United States
GR  - P50CA097190/CA/NCI NIH HHS/United States
GR  - R01DE016086/DE/NIDCR NIH HHS/United States
GR  - R01DE14729/DE/NIDCR NIH HHS/United States
GR  - R25CA089507/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (H2AX protein, human)
RN  - 0 (Histones)
RN  - 0 (MRE11 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.- (MRE11 Homologue Protein)
SB  - IM
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Carcinoma, Squamous Cell/*genetics
MH  - Cell Cycle Proteins/genetics
MH  - Cell Line, Tumor
MH  - *Chromosome Deletion
MH  - *Chromosomes, Human, Pair 11
MH  - DNA Repair-Deficiency Disorders/*genetics
MH  - DNA-Binding Proteins/deficiency/genetics
MH  - Gene Amplification
MH  - Head and Neck Neoplasms/*genetics
MH  - Histones/deficiency/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - MRE11 Homologue Protein
MH  - Protein Serine-Threonine Kinases/deficiency/genetics
MH  - *Radiation, Ionizing
MH  - Tumor Suppressor Proteins/deficiency/genetics
EDAT- 2007/05/12 09:00
MHDA- 2007/08/31 09:00
CRDT- 2007/05/12 09:00
PHST- 2007/05/12 09:00 [pubmed]
PHST- 2007/08/31 09:00 [medline]
PHST- 2007/05/12 09:00 [entrez]
AID - 10.1002/gcc.20462 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2007 Aug;46(8):761-75. doi: 10.1002/gcc.20462.