Transcriptomics,Genomics

Dataset Information

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Highly Aneuploid Zebrafish Malignant Peripheral Nerve Sheath Tumors have Genetic Alterations Similar to Human Cancers


ABSTRACT: Aneuploidy is a hallmark of human cancers, but most mouse cancer models lack the extensive aneuploidy seen in many human tumors. The zebrafish is becoming an increasingly popular model for studying cancer. Here we report that malignant peripheral nerve sheath tumors (MPNSTs) that arise in zebrafish as a result of mutations in either ribosomal protein (rp) genes or in p53 are highly aneuploid. Karyotyping reveals that these tumors frequently harbor near-triploid numbers of chromosomes, and they vary in chromosome number from cell-to-cell within a single tumor. Using array CGH (aCGH) we found that, as in human cancers, certain fish chromosomes are preferentially over-represented while others are under-represented in many MPNSTs. In addition, we detected evidence for recurrent sub-chromosomal amplifications and deletions that may contain genes involved in cancer initiation or progression. One striking amplification included the c-met proto-oncogene. Our results suggest that the zebrafish may be a valuable model in which to study aneuploidy in human cancer and in which to identify candidate genes that may act as drivers in fish and potentially also in human tumors. For GSM587250-GSM587255: This Illumina sequencing data is for validation of a larger array-CGH dataset (GSM580580-GSM580621). For GSM580580-GSM580621: Two-condition (x3) experiment: (1) genomic DNA: MPNST (rp gene mutation) vs normal tail : 31 replicates; (2) MPNST (p53 mutation) vs normal tail: 5 replicates; (3) normal tail vs. normal tail (6 replicates) For GSM587250-GSM587255: Six samples total, in three pairs of tumor (MPNST) and normal tail control

ORGANISM(S): Danio rerio  

SUBMITTER: Nancy Hopkins   Adam Amsterdam  GuangJun Zhang  Jacqueline A Lees  Sebastian Hoersch  Charles A Whittaker 

PROVIDER: E-GEOD-23666 | ArrayExpress | 2010-09-08

SECONDARY ACCESSION(S): GSE23666SRP003498PRJNA130823

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Highly aneuploid zebrafish malignant peripheral nerve sheath tumors have genetic alterations similar to human cancers.

Zhang Guangjun G   Hoersch Sebastian S   Amsterdam Adam A   Whittaker Charles A CA   Lees Jacqueline A JA   Hopkins Nancy N  

Proceedings of the National Academy of Sciences of the United States of America 20100913 39


Aneuploidy is a hallmark of human cancers, but most mouse cancer models lack the extensive aneuploidy seen in many human tumors. The zebrafish is becoming an increasingly popular model for studying cancer. Here we report that malignant peripheral nerve sheath tumors (MPNSTs) that arise in zebrafish as a result of mutations in either ribosomal protein (rp) genes or in p53 are highly aneuploid. Karyotyping reveals that these tumors frequently harbor near-triploid numbers of chromosomes, and they v  ...[more]

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