Alterations of the INK4a/ARF locus in human intracranial germ cell tumors

Masayuki Iwato, Osamu Tachibana, Yasuo Tohma, Yasuaki Arakawa, Hisashi Nitta, Mitsuhiro Hasegawa, Junkoh Yamashita, Yutaka Hayashi

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Little is known about the molecular mechanisms responsible for the development of intracranial germ cell tumors (ICGTs). Recently, we demonstrated that the balance of the p53-mdm2 interactions is disrupted in ICGTs. The p14(ARF) product, a tumor suppresser gene located on the INK4a/ARF locus, acts as one of the major factors affecting p53-mdm2 interactions via its binding to mdm2 and the stimulation of mdm2 degradation. To evaluate whether genetic alterations of the INK4a/ARF locus occur in the genesis of ICGTs, we analyzed the INK4a/ARF genes in 21 ICGTs - 10 pure germinomas and 11 nongerminomatous germ cell tumors. Fifteen (71%) of the 21 ICGTs displayed genetic alterations, including 14 homozygous deletions and I frameshift mutation. Furthermore, the frequency of the alterations was higher in pure germinomas [9 (90%) of the 10] than in nongerminomatous germ cell tumors [6 (55%) of the 11; P = 0.09]. These data suggested that INK4a/ARF gene abnormalities could play an important role in the genesis of ICGTs, especially in pure germinoma.

Original languageEnglish
Pages (from-to)2113-2115
Number of pages3
JournalCancer Research
Volume60
Issue number8
Publication statusPublished - 15-04-2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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