The FHIT gene has been implicated as a tumor suppressor gene in human
malignancies. To determine if FHIT alterations play a role in human sq
uamous cell carcinogenesis of the head and neck (HNSCC), we examined t
he gene and its product by RT-PCR, SSCP, Northern, Southern, and Weste
rn blot analysis in primary HNSCC and/or HNSCC cell lines. Three of 32
tumor samples lacked detectable expression of FHIT by RT-PCR but show
ed amplification of a control gene of similar size. One of 29 primary
tumors and 2/9 HNSCC cell lines exhibited aberrant transcripts generat
ed by RT-PCR methods using one set of 40 cycles of amplification. FHIT
mRNA expression was absent in seven HNSCC cell lines but detectable i
n primary keratinocytes by Northern analysis. Using specific polyclona
l antiserum to the full-length I;HIT protein in immunoblot analyses, 4
/9 cell lines analysed showed no expression of pFhit, two exhibited lo
w levels of expression, and three expressed a putative truncated pFhit
. One of 15 tumors analysed also exhibited an overexpressed truncated
protein. PCR/SSCP and Southern analysis of one cell line DNA that expr
essed a truncated protein indicated that it sustained homozygous loss
of FHIT exon 5. Our results suggest that alterations in FHIT at the DN
A, RNA, and protein levels exist at a low but significant frequency in
HNSCCs. Further studies regarding the potential biological activity o
f FHIT are needed to clarify the role of this gene in HIVSCC tumorigen
esis.