Open AccessIndependent Molecular Development of Metachronous Glioblastomas with Extended Intervening Recurrence‐free Interval
Author(s) -
Martinez Ramon,
Schackert HansK.,
Kannen Stephanie,
Lichter Peter,
Joos Stefan,
Schackert Gabriele
Publication year - 2003
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2003.tb00488.x
Subject(s) - pten , cdkn2a , cancer research , mutation , biology , glioblastoma , comparative genomic hybridization , exon , gene , genetics , microbiology and biotechnology , genome , pi3k/akt/mtor pathway , apoptosis
Two metachronous glioblastomas with different cerebral locations in a 53‐year‐old long‐term survival patient were analyzed by multiple genetic approaches. Using comparative genomic hybridization a different pattern of chromosomal aberrations was observed, with 19 imbalances in the first tumor and only 2 imbalances in the second. Sequence analysis revealed a distinct mutation profile in each tumor, with amino acid substitutions in the p53 and PTEN genes only in the first tumor, ie, p53 in codon 273 (CGT→TGT, Arg→Cys) and PTEN in codon 336 (TAC→TTC, Tyr→Phe). A splicing acceptor site PTEN mutation (IVS8‐2A>G) was observed only in the second GBM. EGFR amplification, mutations of p16 INK4a / CDKN2A or p14 ARF were not observed. According to the results of p53 mutational analysis and EGFR amplification studies, the first tumor is classified as a type 1 GBM, whereas the alterations in the second one are different from those typically encountered in type 1 or type 2 tumors. In conclusion, our data strongly suggest that the metachronous tumors in this patient are exceptional in that they developed independently from each other. Whether the molecular features of the first glioblastoma are associated with the notably extended recurrence‐free period of 5 years remains to be elucidated.