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Distinct cytogenetic pathways of advanced‐stage neuroblastoma tumors, detected by spectral karyotyping
Author(s) -
Stark Batia,
Jeison Marta,
BarAm Irit,
GlaserGabay Leticia,
Mardoukh Jacques,
Luria Drorit,
Feinmesser Meora,
Goshen Yacov,
Stein Jerry,
Abramov Aya,
Zaizov Rina,
Yaniv Isaac
Publication year - 2002
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10082
Subject(s) - chromosomal translocation , karyotype , biology , metaphase , chromosome , cytogenetics , neuroblastoma , fluorescence in situ hybridization , comparative genomic hybridization , genetics , molecular cytogenetics , microbiology and biotechnology , gene , cell culture
Abstract Molecular studies of advanced‐stage neuroblastoma (NBL) have revealed a marked genetic heterogeneity. In addition to MYCN amplification and chromosome 1 short‐arm deletions/translocations detected by conventional cytogenetics, application of fluorescence in situ hybridization has disclosed a high prevalence of 17q gain, whereas allelotyping and comparative genomic hybridization techniques also have revealed loss of 11q and of other chromosomal material. Using the recently developed technique of spectral karyotyping (SKY), we sought to refine the cytogenetic information, identify hidden recurrent structural chromosomal abnormalities, and compare them to the molecular findings. Thirteen samples of metaphase spreads from 11 patients with advanced‐stage NBL were analyzed by SKY. Most of them were found to have complex karyotypes (more than three changes per metaphase) and complex unbalanced rearrangements. Recurrent aberrations leading to 17q gain, deletion of 1p, MYCN amplification, and loss of 11q appeared in 7, 4, 4, and 5 patients, respectively, in simple and complex karyotypes. Chromosome 3 changes and gain of 1q and 7q appeared in 6, 5, and 4 patients, respectively, in complex karyotypes only, reflecting later changes. A strikingly high prevalence of the unbalanced translocation der(11)t(11;17), leading to concomitant 11q loss and 17q gain in 4 patients, delineated a distinct cytogenetic group, none having 1p deletion and/or MYCN amplification. der(11)t(11;17) was associated with complex karyotypes with changes in chromosomes 3 and 7q. The 17q translocations with partners other than 11q were associated with 1p deletion and/or MYCN amplification. The distinct cytogenetic subgroups identified by SKY confirm and extend the recent molecular observations, and suggest that different genes may interact in the der(11)t(11;17) pathway of NBL development and progression. © 2002 Wiley‐Liss, Inc.