In:
Genes, Chromosomes and Cancer, Wiley, Vol. 45, No. 4 ( 2006-04), p. 401-410
Kurzfassung:
Medulloblastoma is a highly malignant embryonal tumor of the cerebellum that accounts for 20%–25% of all intracranial pediatric tumors. The most frequent chromosomal rearrangement in medulloblastoma is isochromosome 17, or i(17q). Its frequency suggests that it serves an important role in tumor pathogenesis, possibly mediated by the disruption or permanent activation of a gene at the breakpoint. To address this question, we performed a detailed analysis of chromosome 17 DNA copy number from 18 medulloblastomas previously shown to carry an apparent i(17q). We identified two breakpoint regions, one well within band 17p11.2 ( n = 16) and a second within the pericentromeric region ( n = 2). To map the breakpoints more precisely, we constructed a tiling‐path matrix‐CGH array covering chromosomal band 17p11.2 to the centromere and utilized it to delineate two small breakpoint intervals mapping at Mb 19.0 and 21.7 in seven of the medulloblastomas and in nine hematological neoplasias with i(17q). The former interval contains two breakpoint clusters that each colocalize with a pair of head‐to‐head inverted DNA sequence repeats, and the latter maps close to a region of α‐satellite repeats. No consensus coding sequence localizes in these regions. Together, these data strongly suggest that the effects of i(17q) in medulloblastoma are mediated by gene‐dosage effects of genes on 17p or 17q rather than by the disruption or deregulation of a “breakpoint” gene. Furthermore, we identified artifacts introduced in DNA copy number data by cross‐hybridization of low‐copy repeat sequences and discuss the challenge these can pose in the interpretation of diagnostic microarrays. © 2006 Wiley‐Liss, Inc.
Materialart:
Online-Ressource
ISSN:
1045-2257
,
1098-2264
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2006
ZDB Id:
1018988-9
ZDB Id:
1492641-6
SSG:
12
