Comparative Genomic Hybridization Detects An Increased Number of Chromosomal Alterations in Large Cell/Anaplastic Medulloblastomas

Abstract

We correlate chromosomal changes in medulloblastomas with histologic subtype, reporting the analysis of 33 medulloblastoma specimens by comparative genomic hybridization, and a subset by fluorescence in situ hybridization. Of the 33 tumors, 5 were desmoplastic/nodular, 10 were histologically classic, and 18 were large cell/anaplastic. Chromosomal gains and losses were more common in anaplastic medulloblastomas than in non‐anaplastic ones. We identified 4 medulloblastomas with c‐myc amplification and 5 medulloblastomas with N‐myc amplification; all 9 were of the large cell/anaplastic subtype. Additional regions with high level gains included 2q14‐22, 3p23, 5p14‐pter, 8q24, 9p22‐23, 10p12‐pter, 12q24, 12p11‐12, 17p11‐12, and Xp11. The majority of these high level gains occurred in anaplastic cases. We also found loss of chromosome 17p in 7 large cell/anaplastic cases but no non‐anaplastic medulloblastomas. Finally, we detected a significantly increased overall number of chromosomal alterations in large cell/anaplastic medulloblastomas (6.8/case) compared to non‐anaplastic ones (3.3/case). These findings support an association between myc oncogene amplification, 17p loss, and large cell/anaplastic histology.

Medulloblastoma – Genetic Alterations

“…Using more sophisticated and advanced techniques such as CGH to profile a panel of 27 primary MB (Reardon et al 1997) revealed frequent loss of 10q, 11, 16q, 17p, and 8p as well as recurrent gains of chromosomes 7, and 17q. These losses and gains were also confirmed by other techniques, such as G-banding, SKY and FISH (Aldosari et al 2002;Avet-Loiseau et al 1999 ;Bayani et al 2000;Eberhart et al 2002;Gilhuis et al 2000). Array CGH of 47 MB (Speicher and Carter 2005) showed gain of 17q, 7, and 1q and loss of 17p, 11p,10q and 8.…”

Accumulation of genomic aberrations during clinical progression of medulloblastoma

“…Cytogenetic aberrations in MB involving chromosome 17 as well as ampliWcations of the MYC or MYCN oncogenes have previously been associated with large cell histology and poor patient survival in diVerent studies [6,7,9,11,13,15,17,18,23,24]. In contrast, several recent reports have identiWed monosomy of chromosome 6 to be associated with consecutive WNT pathway activation and favorable clinical outcome [2,8,25].…”

“…Nevertheless, this has been a hypothesis only, because conclusive evidence of temporal molecular MB progression has not been presented yet. Only one study reported on CGH analyses of a single pair of primary MB and its recurrence [6]. In that case, an increased number of overall chromosomal aberrations was found in the recurrent tumor, one of the acquired lesions being a deletion of 17p.…”

Molecular cytogenetic analysis in the study of brain tumors: findings and applications

“…Amplifications were detected in this group at 2p24 (14.3%) and 9p (14.3%). Among the 18 desmoplastic medulloblastomas, 13,73,87 no amplifications were detected and losses predominated over gains, particularly the losses of chromosomes 6, 10q23-qter, 11, 14, and 19. Gains were detected primarily on chromosomes 7 and 17q.…”

“…Molecular cytogenetic analysis in the study of brain tumors In the 40 tumors identified as medulloblastomas (NOS), 13,73,87,178,250 the patterns of gains and losses were similar to the cumulative profile; however, amplifications were not identified in this group. Among the 14 lesions designated as PNETs (not otherwise specified), 13,263 gains were identified at 1 (7.1%) or 1q (14.1%), 2p (7.1%), 3q (14.3%), 6 (14.3%), 6p (6%), 7 (42%), 7q (15%), 8q (14.3%), 10p (14.3%), 14 (14.3%), 16 (7.1%), 16q21-qter (21.4%), 17 (35%), 18 (24%), 20q (28%), and 22 (71%); and losses were seen at 4q (14%), 10q23-10qter (7.3%), 12 (28%), and 19 (7.1%).…”