PMID- 12925955
OWN - NLM
STAT- MEDLINE
DCOM- 20031009
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 107
IP  - 1
DP  - 2003 Oct 20
TI  - Spindle assembly checkpoint defects and chromosomal instability in head and neck 
      squamous cell carcinoma.
PG  - 46-52
AB  - Alterations in chromosomal number and structure are found in most solid 
      malignancies including head and neck squamous cell carcinoma (HNSC), however, the 
      presence of ongoing, chromosomal instability in HNSC and its relation to spindle 
      assembly checkpoint defects has not been formally demonstrated. We investigated 
      the status of chromosomal instability (CIN) in HNSC primary tumors and cell lines 
      as well as spindle assembly checkpoint integrity in HNSC cell lines. Centromeric 
      fluorescence in situ hybridization (FISH) was carried out on expanded single 
      cell-derived colonies from HNSC cell lines and primary HNSC touch preparations. 
      The deviation of chromosomes from the modal number in single cell derived 
      colonies was 18.4-27% in 6 HNSC cell lines, and 2-3% in a control cell line, 
      HCT116. Twelve primary tumors and 4 normal controls were also studied; all 
      primary tumors demonstrated significant deviation from the modal chromosomal 
      number (average 33.7%, range = 29.9-43.9%), compared to normal controls (average 
      4.6%, range = 3.6-5.6%). Additional characterization of the rate of chromosomal 
      breakage was carried out by dual color FISH simultaneously using centromeric and 
      telomeric probes for individual chromosomes on expanded singe cell-derived 
      colonies and primary HNSC. Control HCT 116 colonies demonstrated a mean 
      discordance between number of centromeric and telomeric hybridization signals in 
      21% (range = 19-23%) of cells, whereas HNSC cell line colonies demonstrated a 
      mean discordance of 50% (range = 38-55%), with the majority of instances of 
      discordant signal indicating telomeric loss. Similarly, touch preparations from 
      primary HNSC demonstrated discordance in hybridization signal of centromeric vs. 
      telomeric signal of 26.3% (range = 18.5-42%), with normal controls showing a rate 
      of discordance of 6.4% (range = 4-8%). Finally, all 6 HNSC cell lines 
      demonstrated partial impairment of mitotic arrest in response to nocodazole, 
      indicating that impairment of the spindle assembly checkpoint may contribute to 
      chromosomal instability in HNSC. Ongoing instability in chromosomal number and 
      structure are consistent features of primary HNSC and cell lines. Spindle 
      assembly checkpoint impairment occurs in HNSC cell lines and may contribute to 
      chromosomal instability in HNSC.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Minhas, Khalid M
AU  - Minhas KM
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, 
      Baltimore, MD, USA.
FAU - Singh, Bhuvanesh
AU  - Singh B
FAU - Jiang, Wei-Wen
AU  - Jiang WW
FAU - Sidransky, David
AU  - Sidransky D
FAU - Califano, Joseph A
AU  - Califano JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (DNA, Neoplasm)
SB  - IM
MH  - Carcinoma, Squamous Cell/*genetics
MH  - Centrosome
MH  - *Chromosome Aberrations
MH  - Chromosomes/genetics
MH  - DNA, Neoplasm/analysis
MH  - Head and Neck Neoplasms/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Mitosis
MH  - Spindle Apparatus/*genetics
MH  - Tumor Cells, Cultured
EDAT- 2003/08/20 05:00
MHDA- 2003/10/10 05:00
CRDT- 2003/08/20 05:00
PHST- 2003/08/20 05:00 [pubmed]
PHST- 2003/10/10 05:00 [medline]
PHST- 2003/08/20 05:00 [entrez]
AID - 10.1002/ijc.11341 [doi]
PST - ppublish
SO  - Int J Cancer. 2003 Oct 20;107(1):46-52. doi: 10.1002/ijc.11341.