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Open AccessArticle

BRCA2 Deletion Induces Alternative Lengthening of Telomeres in Telomerase Positive Colon Cancer Cells

1
Oncogenomic and Epigenetic Unit, IRCSS Regina Elena National Cancer Institute, Via Elio Chianesi, 53-00144 Rome, Italy
2
Biology and Biotechnology Department “Charles Darwin”, Sapienza University of Rome, Piazzale Aldo Moro, 5-00185 Rome, Italy
3
Institute of Molecular Biology and Pathology, CNR, Via degli Apuli, 4-00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Genes 2019, 10(9), 697; https://doi.org/10.3390/genes10090697
Received: 24 June 2019 / Revised: 16 August 2019 / Accepted: 3 September 2019 / Published: 10 September 2019
(This article belongs to the Special Issue ALT: From Telomere Maintenance Mechanisms to Proposed Therapies)
BRCA1/2 are tumor suppressor genes controlling genomic stability also at telomeric and subtelomeric loci. Their mutation confers a predisposition to different human cancers but also sensitivity to antitumor drugs including poly(ADP-ribose) polymerase (PARP) inhibitors and G-quadruplex stabilizers. Here we demonstrate that BRCA2 deletion triggers TERRA hyperexpression and alternative lengthening mechanisms (ALT) in colon cancer cells in presence of telomerase activity. This finding opens the question if cancer patients bearing BRCA2 germline or sporadic mutation are suitable for anti-telomerase therapies, or how ALT activation could influence the short or long-term response to anti-PARP inhibitors or anti-G-quadruplex therapies. View Full-Text
Keywords: BRCA2 mutation; telomeres; ALT BRCA2 mutation; telomeres; ALT
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Pompili, L.; Maresca, C.; Dello Stritto, A.; Biroccio, A.; Salvat, E. BRCA2 Deletion Induces Alternative Lengthening of Telomeres in Telomerase Positive Colon Cancer Cells. Genes 2019, 10, 697.

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