A deterministic analysis of genome integrity during neoplastic growth in Drosophila.

The development of cancer has been associated with the gradual acquisition of genetic alterations leading to a progressive increase in malignancy. In various cancer types this process is enabled and accelerated by genome instability. While genome sequencing-based analysis of tumor genomes becomes in...

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Autores principales:	Cem Sievers, Federico Comoglio, Makiko Seimiya, Gunter Merdes, Renato Paro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d76e795dc4dc4c11936a884ac0d3b927
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spelling	oai:doaj.org-article:d76e795dc4dc4c11936a884ac0d3b9272021-11-18T08:33:30ZA deterministic analysis of genome integrity during neoplastic growth in Drosophila.1932-620310.1371/journal.pone.0087090https://doaj.org/article/d76e795dc4dc4c11936a884ac0d3b9272014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24516544/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The development of cancer has been associated with the gradual acquisition of genetic alterations leading to a progressive increase in malignancy. In various cancer types this process is enabled and accelerated by genome instability. While genome sequencing-based analysis of tumor genomes becomes increasingly a standard procedure in human cancer research, the potential necessity of genome instability for tumorigenesis in Drosophila melanogaster has, to our knowledge, never been determined at DNA sequence level. Therefore, we induced formation of tumors by depletion of the Drosophila tumor suppressor Polyhomeotic and subjected them to genome sequencing. To achieve a highly resolved delineation of the genome structure we developed the Deterministic Structural Variation Detection (DSVD) algorithm, which identifies structural variations (SVs) with high accuracy and at single base resolution. The employment of long overlapping paired-end reads enables DSVD to perform a deterministic, i.e. fragment size distribution independent, identification of a large size spectrum of SVs. Application of DSVD and other algorithms to our sequencing data reveals substantial genetic variation with respect to the reference genome reflecting temporal separation of the reference and laboratory strains. The majority of SVs, constituted by small insertions/deletions, is potentially caused by erroneous replication or transposition of mobile elements. Nevertheless, the tumor did not depict a loss of genome integrity compared to the control. Altogether, our results demonstrate that genome stability is not affected inevitably during sustained tumor growth in Drosophila implying that tumorigenesis, in this model organism, can occur irrespective of genome instability and the accumulation of specific genetic alterations.Cem SieversFederico ComoglioMakiko SeimiyaGunter MerdesRenato ParoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e87090 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cem Sievers Federico Comoglio Makiko Seimiya Gunter Merdes Renato Paro A deterministic analysis of genome integrity during neoplastic growth in Drosophila.
description	The development of cancer has been associated with the gradual acquisition of genetic alterations leading to a progressive increase in malignancy. In various cancer types this process is enabled and accelerated by genome instability. While genome sequencing-based analysis of tumor genomes becomes increasingly a standard procedure in human cancer research, the potential necessity of genome instability for tumorigenesis in Drosophila melanogaster has, to our knowledge, never been determined at DNA sequence level. Therefore, we induced formation of tumors by depletion of the Drosophila tumor suppressor Polyhomeotic and subjected them to genome sequencing. To achieve a highly resolved delineation of the genome structure we developed the Deterministic Structural Variation Detection (DSVD) algorithm, which identifies structural variations (SVs) with high accuracy and at single base resolution. The employment of long overlapping paired-end reads enables DSVD to perform a deterministic, i.e. fragment size distribution independent, identification of a large size spectrum of SVs. Application of DSVD and other algorithms to our sequencing data reveals substantial genetic variation with respect to the reference genome reflecting temporal separation of the reference and laboratory strains. The majority of SVs, constituted by small insertions/deletions, is potentially caused by erroneous replication or transposition of mobile elements. Nevertheless, the tumor did not depict a loss of genome integrity compared to the control. Altogether, our results demonstrate that genome stability is not affected inevitably during sustained tumor growth in Drosophila implying that tumorigenesis, in this model organism, can occur irrespective of genome instability and the accumulation of specific genetic alterations.
format	article
author	Cem Sievers Federico Comoglio Makiko Seimiya Gunter Merdes Renato Paro
author_facet	Cem Sievers Federico Comoglio Makiko Seimiya Gunter Merdes Renato Paro
author_sort	Cem Sievers
title	A deterministic analysis of genome integrity during neoplastic growth in Drosophila.
title_short	A deterministic analysis of genome integrity during neoplastic growth in Drosophila.
title_full	A deterministic analysis of genome integrity during neoplastic growth in Drosophila.
title_fullStr	A deterministic analysis of genome integrity during neoplastic growth in Drosophila.
title_full_unstemmed	A deterministic analysis of genome integrity during neoplastic growth in Drosophila.
title_sort	deterministic analysis of genome integrity during neoplastic growth in drosophila.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d76e795dc4dc4c11936a884ac0d3b927
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A deterministic analysis of genome integrity during neoplastic growth in Drosophila.

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