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

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35 Citations (Scopus)


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
Issue number8
Publication statusPublished - 15-04-2000

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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