Background. Deletion of 9p21 is a common event in many human tumors, i
ncluding 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 thes
e 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 prospe
ctive survival analysis. Results. We demonstrate that LOH of 9p and, s
pecifically, the interferon (IFN) gene cluster correlates with recurre
nce of HNSCC. We also demonstrate two separate areas of deletion on 9p
, one centromeric to IFN beta and telomeric to CDKN2 and the other cen
tromeric to CDKN2 and telomeric to the polymorphic marker D9S19. All t
he deletions involve either the markers IFN alpha and/or D9S171 and D9
S126 but not necessarily CDKN2. Conclusions. These results suggest ano
ther tumor suppressor gene (TSG) may be involved in HNSCC carcinogenes
is and may play a role in aggressive disease as manifest by local, reg
ional, or distant recurrence. (C) 1998 John Wiley & Sons, Inc.