9p21 deletion correlates with recurrence in head and neck cancer.
BACKGROUND
Deletion of 9p21 is a common event in many human tumors, including head and neck squamous cell carcinoma (HNSCC). The gene CDKN2, which encodes the protein p16, a cyclin-dependent kinase-4 inhibitor, maps to 9p21. The role of CDKN2 as the tumor suppressor gene in these neoplasms is unclear. The role of loss of heterozygosity (LOH) as a prognostic tool has not been described in HNSCC.


METHODS
We performed deletion mapping using Southern and PCR-based LOH analysis and prospective survival analysis.


RESULTS
We demonstrate that LOH of 9p and, specifically, the interferon (IFN) gene cluster correlates with recurrence of HNSCC. We also demonstrate two separate areas of deletion on 9p, one centromeric to IFNbeta and telomeric to CDKN2 and the other centromeric to CDKN2 and telomeric to the polymorphic marker D9S19. All the deletions involve either the markers IFNalpha and/or D9S171 and D9S126 but not necessarily CDKN2.


CONCLUSIONS
These results suggest another tumor suppressor gene (TSG) may be involved in HNSCC carcinogenesis and may play a role in aggressive disease as manifest by local, regional, or distant recurrence.
Lydiatt
W M
WM
Department of Otolaryngology-Head and Neck Surgery, University of Nebraska Medical Center and Methodist Hospital, Omaha 68198-1225, USA.
Davidson
B J
BJ
Schantz
S P
SP
Caruana
S
S
Chaganti
R S
RS
D000368:Aged; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002503:Centromere / Q000235:genetics; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics; D019942:Genes, p16 / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics; D007372:Interferons / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D016615:Telomere / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers; D016899:Interferon-beta; D007372:Interferons