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Evidence of Genetic Instability in Tumors and Normal Nearby Tissues

BACKGROUND: Comprehensive analyses have recently been performed on many human cancer tissues, leading to the identification of a number of mutated genes but providing no information on the variety of mutations present in each of them. This information is of interest to understand the possible origin...

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Autores principales: Geraci, Giuseppe, D'Elia, Ida, del Gaudio, Rosanna, Di Giaimo, Rossella
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826410/
https://www.ncbi.nlm.nih.gov/pubmed/20186333
http://dx.doi.org/10.1371/journal.pone.0009343
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author Geraci, Giuseppe
D'Elia, Ida
del Gaudio, Rosanna
Di Giaimo, Rossella
author_facet Geraci, Giuseppe
D'Elia, Ida
del Gaudio, Rosanna
Di Giaimo, Rossella
author_sort Geraci, Giuseppe
collection PubMed
description BACKGROUND: Comprehensive analyses have recently been performed on many human cancer tissues, leading to the identification of a number of mutated genes but providing no information on the variety of mutations present in each of them. This information is of interest to understand the possible origin of gene mutations that cause tumors. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the sequence heterogeneity of the transcripts of the human HPRT and G6PD single copy genes that are not considered tumor markers. Analyses have been performed on different colon cancers and on the nearby histologically normal tissues of two male patients. Several copies of each cDNA, which were produced by cloning the RT-PCR-amplified fragments of the specific mRNA, have been sequenced. Similar analyses have been performed on blood samples of two ostensibly healthy males as reference controls. The sequence heterogeneity of the HPRT and G6PD genes was also determined on DNA from tumor tissues. The employed analytical approach revealed the presence of low-frequency mutations not detectable by other procedures. The results show that genetic heterogeneity is detectable in HPRT and G6PD transcripts in both tumors and nearby healthy tissues of the two studied colon tumors. Similar frequencies of mutations are observed in patient genomic DNA, indicating that mutations have a somatic origin. HPRT transcripts show genetic heterogeneity also in healthy individuals, in agreement with previous results on human T-cells, while G6PD transcript heterogeneity is a characteristic of the patient tissues. Interestingly, data on TP53 show little, if any, heterogeneity in the same tissues. CONCLUSIONS/SIGNIFICANCE: These findings show that genetic heterogeneity is a peculiarity not only of cancer cells but also of the normal tissue where a tumor arises.
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spelling pubmed-28264102010-02-26 Evidence of Genetic Instability in Tumors and Normal Nearby Tissues Geraci, Giuseppe D'Elia, Ida del Gaudio, Rosanna Di Giaimo, Rossella PLoS One Research Article BACKGROUND: Comprehensive analyses have recently been performed on many human cancer tissues, leading to the identification of a number of mutated genes but providing no information on the variety of mutations present in each of them. This information is of interest to understand the possible origin of gene mutations that cause tumors. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the sequence heterogeneity of the transcripts of the human HPRT and G6PD single copy genes that are not considered tumor markers. Analyses have been performed on different colon cancers and on the nearby histologically normal tissues of two male patients. Several copies of each cDNA, which were produced by cloning the RT-PCR-amplified fragments of the specific mRNA, have been sequenced. Similar analyses have been performed on blood samples of two ostensibly healthy males as reference controls. The sequence heterogeneity of the HPRT and G6PD genes was also determined on DNA from tumor tissues. The employed analytical approach revealed the presence of low-frequency mutations not detectable by other procedures. The results show that genetic heterogeneity is detectable in HPRT and G6PD transcripts in both tumors and nearby healthy tissues of the two studied colon tumors. Similar frequencies of mutations are observed in patient genomic DNA, indicating that mutations have a somatic origin. HPRT transcripts show genetic heterogeneity also in healthy individuals, in agreement with previous results on human T-cells, while G6PD transcript heterogeneity is a characteristic of the patient tissues. Interestingly, data on TP53 show little, if any, heterogeneity in the same tissues. CONCLUSIONS/SIGNIFICANCE: These findings show that genetic heterogeneity is a peculiarity not only of cancer cells but also of the normal tissue where a tumor arises. Public Library of Science 2010-02-23 /pmc/articles/PMC2826410/ /pubmed/20186333 http://dx.doi.org/10.1371/journal.pone.0009343 Text en Geraci et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Geraci, Giuseppe
D'Elia, Ida
del Gaudio, Rosanna
Di Giaimo, Rossella
Evidence of Genetic Instability in Tumors and Normal Nearby Tissues
title Evidence of Genetic Instability in Tumors and Normal Nearby Tissues
title_full Evidence of Genetic Instability in Tumors and Normal Nearby Tissues
title_fullStr Evidence of Genetic Instability in Tumors and Normal Nearby Tissues
title_full_unstemmed Evidence of Genetic Instability in Tumors and Normal Nearby Tissues
title_short Evidence of Genetic Instability in Tumors and Normal Nearby Tissues
title_sort evidence of genetic instability in tumors and normal nearby tissues
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826410/
https://www.ncbi.nlm.nih.gov/pubmed/20186333
http://dx.doi.org/10.1371/journal.pone.0009343
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