Alternative Lengthening of Telomeres in Neuroblastoma Cell Lines is Associated with a Lack of MYCN Genomic Amplification and with P53 Pathway Aberrations

Overview

Journal J Neurooncol

Publisher Springer

Date 2014 May 6

PMID 24792489

Citations 22

Authors

Ahsan S Farooqi

Rebecca A Dagg

L Mi Rim Choi

Jerry W Shay

C Patrick Reynolds

Loretta M S Lau

Affiliations

Soon will be listed here.

Abstract

Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere length maintenance mechanism that enables the unlimited proliferation of a subset of cancer cells. Some neuroblastoma (NB) tumors appear to maintain telomere length by activating ALT. Of 40 NB cell lines, we identified four potential ALT cell lines (CHLA-90, SK-N-FI, LA-N-6, and COG-N-291) that were telomerase-negative and had long telomeres (a feature of ALT cells). All four cell lines lacked MYCN amplification and were p53 non-functional upon irradiation. Two of these cell lines (CHLA-90 and SK-N-FI) were positive for C-circles (telomeric DNA circles) and ALT-associated promyelocytic leukemia nuclear bodies, both of which are phenotypic characteristics of ALT. Mutation of ATRX (associated with ALT in tumors) was only found in CHLA-90. Thus, the ALT phenotype in NB may not be limited to tumors with ATRX mutations but is associated with a lack of MYCN amplification and alterations in the p53 pathway.

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