Loss of p16 (INK4A) expression is associated with allelic imbalance/loss of heterozygosity of chromosome 9p21 in microdissected malignant peripheral nerve sheath tumors.

The p16 is a tumor suppressor gene on the short arm of chromosome 9p21. The product of the p16 acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein. This study was designed to assess the frequency of genetic loss of 9p21 and to determine the role of p16 the pathogenesis of sporadic and neurofibromatosis 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs). The authors examined 15 cases for p16 protein expression and 10 cases for allelic imbalance (AI)/loss of heterozygosity (LOH) of chromosome 9p. DNA was microdissected from normal and neoplastic tissues. AI/LOH analysis was performed using six microsatellite markers on the 9p region. On immunohistochemical analysis 80% of cases showed abnormal expression of p16. Similarly, 8 of 10 cases revealed genetic loss with at least one microsatellite marker. The most frequent deletion was that within the coding sequence. Of p16 at me D9S974 locus. These findings emphasize the role of loss of p16 in the development of both sporadic and NF1-associated MPNSTs.