TY - JOUR
T1 - Frequent inactivation of p16(INK4α) in oral premalignant lesions
AU - Papadimitrakopoulou, Vali
AU - Izzo, Julie
AU - Lippman, Scott M.
AU - Lee, Jin Soo
AU - Fan, You Hong
AU - Clayman, Gary
AU - Ro, Jay Y.
AU - Hittelman, Walter N.
AU - Lotan, Reuben
AU - Hong, Waun K.
AU - Mao, Li
PY - 1997
Y1 - 1997
N2 - Head and neck carcinogenesis is believed to be a multistep process, whereby genetic events accumulate in the carcinogen-exposed field at risk, resulting in distinct phenotypic premalignant changes that eventually evolve into invasive cancer. Frequent loss of heterozygosity (LOH) at the chromosome 9p21 region and inactivation of p16(INK4α) by different mechanisms have been described in head and neck squamous cell carcinoma (HNSCC). Recently, we reported that loss of 9p21 is also frequent in oral premalignant lesions. To investigate potential inactivation of p16(INK4α) in these premalignant lesions, we analysed 74 biopsies from 36 patients by immunohistochemistry (IHC) for expression of the p16 protein. Loss of p16 expression was found in 28 (38%) of the lesion biopsies from 17 patients (47%). LOH at the D9s171, a marker in the 9p21 region, was observed in 19 lesion biopsies from 12 cases and correlated with absence of p16 by IHC in 11 (92%) of the 12 comparable cases and 15 (79%) of 19 lesion biopsies. By direct sequencing of ten lesion biopsies from ten individuals with LOH at D9s171 for p16(INK4α) exon 2, one non-sense mutation at codon 88 (GGA→TGA) was identified. Our data suggest that inactivation of p16(INK4α) may play an important role in early head and neck cancer development.
AB - Head and neck carcinogenesis is believed to be a multistep process, whereby genetic events accumulate in the carcinogen-exposed field at risk, resulting in distinct phenotypic premalignant changes that eventually evolve into invasive cancer. Frequent loss of heterozygosity (LOH) at the chromosome 9p21 region and inactivation of p16(INK4α) by different mechanisms have been described in head and neck squamous cell carcinoma (HNSCC). Recently, we reported that loss of 9p21 is also frequent in oral premalignant lesions. To investigate potential inactivation of p16(INK4α) in these premalignant lesions, we analysed 74 biopsies from 36 patients by immunohistochemistry (IHC) for expression of the p16 protein. Loss of p16 expression was found in 28 (38%) of the lesion biopsies from 17 patients (47%). LOH at the D9s171, a marker in the 9p21 region, was observed in 19 lesion biopsies from 12 cases and correlated with absence of p16 by IHC in 11 (92%) of the 12 comparable cases and 15 (79%) of 19 lesion biopsies. By direct sequencing of ten lesion biopsies from ten individuals with LOH at D9s171 for p16(INK4α) exon 2, one non-sense mutation at codon 88 (GGA→TGA) was identified. Our data suggest that inactivation of p16(INK4α) may play an important role in early head and neck cancer development.
KW - Head and neck cancer
KW - Immunohistochemistry
KW - Oral premalignant lesions
KW - Pl6(INK4α)
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U2 - 10.1038/sj.onc.1201010
DO - 10.1038/sj.onc.1201010
M3 - Article
C2 - 9150385
AN - SCOPUS:0030612712
VL - 14
SP - 1799
EP - 1803
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 15
ER -