Array comparative genomic hybridization reveals distinct DNA copy number differences between gastrointestinal stromal tumors and leiomyosarcomas

Array comparative genomic hybridization reveals distinct DNA copy number differences between gastrointestinal stromal tumors and leiomyosarcomas

Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation. Until recently, most gastrointestinal stromal tumors (GIST) were also classified as smooth muscle tumors, but now GISTs are recognized as a separate entity, defined as spindle cell and/or epithelioid tumors localized in t...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Vol. 66; no. 18; pp. 8984 - 8993
Main Authors: MEZA-ZEPEDA, Leonardo A, KRESSE, Stine H, BARRAGAN-POLANIA, Ana H, BJERKEHAGEN, Bodil, OHNSTAD, Hege O, NAMLES, Heidi M, JUNBAI WANG, KRISTIANSEN, Bjørn E, MYKLEBOST, Ola
Format: Journal Article
Language:English
Published: Philadelphia, PA American Association for Cancer Research 15-09-2006
Subjects:
Adult
Aged
Animals
Antineoplastic agents
Biological and medical sciences
Chromosome Aberrations
Chromosomes, Human, Pair 17 - genetics
Dermatology
Female
Gastroenterology. Liver. Pancreas. Abdomen
Gastrointestinal Stromal Tumors - genetics
Gene Dosage
Humans
Leiomyosarcoma - genetics
Male
Medical sciences
Mice
Middle Aged
Multigene Family
Nucleic Acid Hybridization - methods
Oligonucleotide Array Sequence Analysis - methods
Pharmacology. Drug treatments
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Transplantation, Heterologous
Tumors
Tumors of the skin and soft tissue. Premalignant lesions
Comparative genomic hybridization
Copy number
DNA
Leiomyosarcoma
DNA chip
Soft tissue sarcoma
Digestive diseases
Smooth muscle
Malignant tumor
Gene expression
Gastrointestinal stromal tumor
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Summary:Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation. Until recently, most gastrointestinal stromal tumors (GIST) were also classified as smooth muscle tumors, but now GISTs are recognized as a separate entity, defined as spindle cell and/or epithelioid tumors localized in the gastrointestinal tract. Using microarray-based comparative genomic hybridization (array CGH), we have created a detailed map of DNA copy number changes for 7 GISTs and 12 leiomyosarcomas. Considerable gains and losses of chromosomal segments were observed in both tumor types. The most frequent aberration observed in GISTs was loss of chromosomes 14 and 22, with minimal recurrent regions in 14q11.2-q32.33 (71% of the tumors) and 22q12.2-q13.31 (100%). In leiomyosarcomas, frequent loss of chromosome 10 and 13q was observed, with minimal recurrent regions in 10q21.3 (75%) and 13q14.2-q14.3 (75%). Recurrent high-level amplification of 17p13.1-p11.2 was detected in leiomyosarcomas. Expression profiling using cDNA microarrays revealed four candidate genes in this region with high expression (AURKB, SREBF1, MFAP4, and FLJ10847). Altered expression of AURKB and SREBF1 has been observed previously in other malignancies. Hierarchical clustering of all samples separated GISTs and leiomyosarcomas into two distinct clusters. Statistical analysis identified six chromosomal regions, 1p36.11-p13.1, 9q21.11-9q34.3, 14q11.2-q23.2, 14q31.3-q32.33, 15q24.3-q26.3, and 22q11.21-q13.31, which were significantly different in copy number between GISTs and leiomyosarcomas. Our results show the potential of using array comparative genomic hybridization to classify histologically similar tumors such as GISTs and leiomyosarcomas.
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ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-06-1972