Two distinct regions of loss on chromosome arm 4q in primary head and neck squamous cell carcinoma.
OBJECTIVE
To more clearly define the frequency and the regions of chromosome arm 4q loss in head and neck squamous cell carcinoma.


METHODS
A retrospective microsatellite analysis of DNA from previously microdissected primary tumor samples.


METHODS
Academic medical center.


METHODS
One hundred primary tumor samples from patients with head and neck squamous cell carcinoma were analyzed for loss of heterozygosity on the long arm of chromosome 4. The Kaplan-Meier method was used to estimate survival for 97 patients for whom clinical data were available. The Cox proportional hazards model was used to compare survival, and logistic regression was used to search for associations between clinical tumor characteristics and 4q status.


RESULTS
Analysis of 33 polymorphic microsatellite markers identified 51 samples (51%) exhibiting loss of heterozygosity of 4q in at least 1 locus. Eighteen tumors revealed loss at all informative markers, indicating monosomy or complete deletion of 4q. Thirty-three tumors displayed partial loss of heterozygosity and delineated 2 minimal areas of loss at 4q2324 and 4q2829. Eleven tumors displayed loss solely at the 4q2324 region, 13 tumors displayed deletions confined to the 4q2829 region, and 9 tumors displayed selective loss at both regions. A separate analysis in a subset of 94 primary head and neck tumors was done to further delineate the minimal area of chromosomal loss at 4q2324. Analysis of 8 markers in this region allowed us to identify the smallest region of loss between markers D4S2986 and D4S1564 (a distance of 2 centimorgans). Review of the clinical records of 97 patients revealed no statistically significant association between 4q status and any clinical variable, including survival.


CONCLUSIONS
These results confirm a high frequency of chromosome arm 4q loss in primary head and neck squamous cell carcinoma and might demarcate 2 novel putative suppressor loci involved in progression of this carcinoma.
Shah
S I
SI
Head and Neck Cancer Research Division, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 720 Rutland Ave, 818 Ross Bldg, Baltimore, MD 21205-2196, USA. dsidrans@jhmi.edu
Yip
L
L
Greenberg
B
B
Califano
J A
JA
Chow
J
J
Eisenberger
C F
CF
Lee
D J
DJ
Sewell
D A
DA
Reed
A L
AL
Lango
M
M
Jen
J
J
Koch
W M
WM
Sidransky
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies