Identification of a novel amplicon at distal 17q containing the BIRC5/SURVIVIN gene in malignant peripheral nerve sheath tumours.
Previous studies have suggested that amplification of genes, notably the TOP2A gene, on chromosome arm 17q may be important for the development of malignant peripheral nerve sheath tumour (MPNST). In order to study the frequency, distribution, and chromosomal organization of rearrangements at 17q, interphase and metaphase fluorescence in situ hybridization (FISH) were used to evaluate copy number changes at 17q in 28 MPNSTs. Increased copy numbers were seen for the ERBB2 and TOP2A genes in eight and nine cases, respectively, supporting a potential role for these two genes in MPNST tumourigenesis. Net gain of distal 17q material was observed in 16 of the 28 MPNSTs, with high-level gain in three cases, and was associated with poor outcome. Among the 26 patients for whom follow-up data were available, gain of distal 17q was present in 11 of 12 tumours that had metastasized, compared with 4 of 14 of those that had not metastasized. Detailed FISH mapping analysis of metaphase spreads identified a 2 Mb commonly gained/amplified region at 17q25. Among the genes mapping to this region, BIRC5, which encodes the baculoviral IAP repeat-containing protein 5/survivin protein, is a strong candidate target gene for amplification, as it has been previously shown to be overexpressed in neurofibromatosis type 1-associated MPNST. Three other genes that co-amplified with BIRC5 represent other potential candidate genes: PTDSR involved in apoptosis; SEPT9 overexpressed in human malignant brain tumours; and SOCS3 involved in cell survival and differentiation of neurons.
Storlazzi
C T
CT
Department of Genetics and Microbiology, University of Bari, Italy. c.storlazzi@biologia.uniba.it
Brekke
H R
HR
Mandahl
N
N
Brosjö
O
O
Smeland
S
S
Lothe
R A
RA
Mertens
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002871:Chromosome Banding; D002886:Chromosomes, Human, Pair 17; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D018628:Gene Dosage; D052138:Genes, Neoplasm; D018734:Genes, erbB-2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051034:Inhibitor of Apoptosis Proteins; D007399:Interphase; D008297:Male; D008677:Metaphase; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000473:pathology; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D004250:DNA Topoisomerases, Type II