Genome-wide high-resolution analysis of DNA copy number alterations in NF1-associated malignant peripheral nerve sheath tumors using 32K BAC array

Mantripragada, Kiran Kumar ORCID: https://orcid.org/0000-0003-2070-8105, de Ståhl, Teresita Díaz, Patridge, Chris, Menzel, Uwe, Andersson, Robin, Chuzhanova, Nadia, Kluwe, Lan, Guha, Abhijit Ranjan, Mautner, Victor, Dumanski, Jan P. and Upadhyaya, Meena 2009. Genome-wide high-resolution analysis of DNA copy number alterations in NF1-associated malignant peripheral nerve sheath tumors using 32K BAC array. Genes, Chromosomes and Cancer 48 (10) , pp. 897-907. 10.1002/gcc.20695

Full text not available from this repository.

Abstract

Neurofibromatosis Type I (NF1) is an autosomal dominant disorder characterized by the development of both benign and malignant tumors. The lifetime risk for developing a malignant peripheral nerve sheath tumor (MPNST) in NF1 patients is �10% with poor survival rates. To date, the molecular basis of MPNST development remains unclear. Here, we report the first genome-wide and high-resolution analysis of DNA copy number alterations in MPNST using the 32K bacterial artificial chromosome microarray on a series of 24 MPNSTs and three neurofibroma samples. In the benign neurofibromas, apart from loss of one copy of the NF1 gene and copy number polymorphisms, no other changes were found. The profiles of malignant samples, however, revealed specific loss of chromosomal regions including 1p35-33, 1p21, 9p21.3, 10q25, 11q22- 23, 17q11, and 20p12.2 as well as gain of 1q25, 3p26, 3q13, 5p12, 5q11.2-q14, 5q21-23, 5q31-33, 6p23-p21, 6p12, 6q15, 6q23-q24, 7p22, 7p14-p13, 7q21, 7q36, 8q22-q24, 14q22, and 17q21-q25. Copy number gains were more frequent than deletions in the MPNST samples (62% vs. 38%). The genes resident within common regions of gain were NEDL1 (7p14), AP3B1 (5q14.1), and CUL1 (7q36.1) and these were identified in >63% MPNSTs. The most frequently deleted locus encompassed CDKN2A, CDKN2B, and MTAP genes on 9p21.3 (33% cases). These genes have previously been implicated in other cancer conditions and therefore, should be considered for their therapeutic, prognostic, and diagnostic relevance in NF1 tumorigenesis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Wiley-Liss Inc
ISSN:	1045-2257
Last Modified:	19 Oct 2022 09:54
URI:	https://orca.cardiff.ac.uk/id/eprint/22588

Citation Data

Cited 46 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item