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Comprehensive SNP array study of frequently used neuroblastoma cell lines; copy neutral loss of heterozygosity is common in the cell lines but uncommon in primary tumors.

Journal article
Authors Hanna Kryh
Helena Carén
Jennie Erichsen
Rose-Marie Sjöberg
Jonas Abrahamsson
Per Kogner
Tommy Martinsson
Published in BMC genomics
Volume 12
Issue 1
Pages 443
ISSN 1471-2164
Publication year 2011
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Institute of Clinical Sciences, Department of Pediatrics
Pages 443
Language en
Links dx.doi.org/10.1186/1471-2164-12-443
https://gup.ub.gu.se/file/62399
Subject categories Medical and Health Sciences

Abstract

ABSTRACT: BACKGROUND: Copy neutral loss of heterozygosity (CN-LOH) refers to a special case of LOH occurring without any resulting loss in copy number. These alterations is sometimes seen in tumors as a way to inactivate a tumor suppressor gene and have been found to be important in several types of cancer. RESULTS: We have used high density single nucleotide polymorphism arrays in order to investigate the frequency and distribution of CN-LOH and other allelic imbalances in neuroblastoma (NB) tumors and cell lines. Our results show that the frequency of these near-CN-LOH events is significantly higher in the cell lines compared to the primary tumors and that the types of CN-LOH differ between the groups. We also show that the low-risk neuroblastomas that are generally considered to have a "triploid karyotype" often present with a complex numerical karyotype (no segmental changes) with 2-5 copies of each chromosome. Furthermore a comparison has been made between the three related cell lines SK-N-SH, SH-EP and SH-SY5Y with respect to overall genetic aberrations, and several aberrations unique to each of the cell lines has been found. CONCLUSIONS: We have shown that the NB tumors analyzed contain several interesting allelic imbalances that would either go unnoticed or be misinterpreted using other genome-wide techniques. These findings indicate that the genetics underlying NB might be even more complex than previously known and that SNP arrays are important analysis tools. We have also showed that these near-CN-LOH events are more frequently seen in NB cell lines compared to NB tumors and that a set of highly related cell lines have continued to evolve secondary to the subcloning event. Taken together our analysis highlights that cell lines in many cases differ substantially from the primary tumors they are thought to represent, and that caution should be taken when drawing conclusions from cell line-based studies.

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