title: Distinct cytogenetic pathways of advanced-stage neuroblastoma tumors, detected by spectral karyotyping.
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.
authors: Cancer Cytogenetic Laboratory, Schneider Children's Medical Center of Israel, Petah Tiqva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. dnaomi@clalit.org.il
authors: Batia
authors: B
authors: Stark
authors: Marta
authors: M
authors: Jeison
authors: Irit
authors: I
authors: Bar-Am
authors: Leticia
authors: L
authors: Glaser-Gabay
authors: Jacques
authors: J
authors: Mardoukh
authors: Drorit
authors: D
authors: Luria
authors: Meora
authors: M
authors: Feinmesser
authors: Yacov
authors: Y
authors: Goshen
authors: Jerry
authors: J
authors: Stein
authors: Aya
authors: A
authors: Abramov
authors: Rina
authors: R
authors: Zaizov
authors: Isaac
authors: I
authors: Yaniv
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019046:Bone Marrow Neoplasms / Q000235:genetics / Q000556:secondary; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary; D002869:Chromosome Aberrations; D020223:Chromosome Painting / Q000379:methods; D020732:Cytogenetic Analysis / Q000379:methods*; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D006580:Genetic Carrier Screening; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008297:Male; D008875:Middle Aged; D009447:Neuroblastoma / Q000235:genetics* / Q000556:secondary; D013125:Spinal Neoplasms / Q000235:genetics* / Q000473:pathology