CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein

Molecular mechanisms of head and neck cancer

“…Increased risk of OSCC has also been reported in individuals inheriting functionally inactivating mutations in the CDKN2A gene. Somatic inactivation of this important regulator of cell cycle at the G1-S boundary has also been reported in sporadic OSCC tumors [27][28][29][30]. The case for the presence of predisposing genetic factors for OSCC is strengthened by the fact that positive family history increases an individual's risk for OSCC by 2-to 4-fold.…”

Functional evaluation of tumour-specific variants of p16INK4a/CDKN2A: correlation with protein structure information

“…An obvious source of concern was that the interaction Yoshida et al, 1995;Sou®r et al, 1998) (Liu et al, 1995) (Zhang et al, 1994;Liu et al, 1995;Pollock et al, 1995;Platz et al, 1997) (Walker et al, 1995;FitzGerald et al, 1996;Flores et al, 1997;Harland et al, 1997;Sun et al, 1997;Sou®r et al, 1998) (Hussussian et al, 1994) (Hayashi et al, 1994;Komiya et al, 1995;Liu et al, 1995;Tamimiet al, 1996) (Hayashi et al, 1994;Mori et al, 1994;Zhang et al, 1994) (Hayashi et al, 1994) (Ohta et al, 1994;Pollock et al, 1995) (Hayashi et al, 1994) (Hussussian et al, 1994;Kamb et al, 1994;Whelan et al, 1995;Sou®r et al, 1998) (Borg et al, 1996;Platz et al, 1997) (Harland et al, 1997) (Yoshida et al, 1995) (Okamoto et al, 1994;Gonzalez-Zulueta et al, 1995;Suzuki et al, 1995) (Hayashi et al, 1994;Marchetti et al, 1997) The variant forms of p16 INK4a are identi®ed by the residue number¯anked by the wild-type and variant amino acids in single letter code. Thus, L16P refers to the substitution of proline for leucine at position 16.…”

“…Only a minority of the known missense variants have been functionally analysed and although the severe loss-offunction mutants are easily detected, a substantial proportion of the variants tested thus far behave ambiguously in di erent assay systems or have given inconsistent results when analysed by di erent laboratories (Koh et al, 1995;Lukas et al, 1995;Ranade et al, 1995;Reymond and Brent, 1995;Shapiro et al, 1995;Wick et al, 1995;Yang et al, 1995;Enders et al, 1996;Lilischkis et al, 1996;Parry and Peters, 1996;Tevelev et al, 1996;Yarbrough et al, 1996;Zhang and Peng, 1996;Arap et al, 1997;Harland et al, 1997;Sun et al, 1997). There are a number of possible reasons.…”

The role of genetic factors in predisposition to squamous cell cancer of the head and neck

“…SCCHN is occasionally featured in several inherited cancer syndromes, including families with hereditary non-polyposis colo-rectal cancer, Fanconi's anaemia, Bloom's syndrome, Xeroderma Pigmentosum and LiFraumeni syndrome (Trizna and Schantz, 1992). P16 germline mutations have been seen in individuals from families with melanoma, pancreatic tumours and SCCHN (Yarbrough et al, 1996;Sun et al, 1997).…”