Involvement of the Ink4a gene (p16 and p19(arf)) in murine tumorigenesis

The INK4A and INK4B genes map to 9p21, with the INK4A gene encoding two pro ducts, p16 and p19(ARF). Many neoplasms in which INK4A and INK4B genes are altered show deletions involving both genes. Mice carrying a targeted Ink4a deletion develop tumors at an early age. In the present study we examined the genetic alterations affecting the remaining Ink4a allele and the Ink4b gene in tumors arising in heterozygous Ink4a mice. We identified deletion o f the remaining Ink4a allele in 7 of 18 (39%) tumors. We also observed dele tion of the exon 1 beta in 3 cases, one of them presenting this deletion as a unique alteration. In conclusion, the deletion of the remaining Ink4a al lele was the alteration most frequently observed, representing the inactiva tion of two proteins capable of arresting the cell cycle through different pathways that involve the tumor suppressors pRB and p53.