The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.

High-grade ovarian serous carcinomas (HGSC) are characterized by TP53 mutations and non-random patterns of chromosomal anomalies, where the nature of the TP53 mutation may correlate with clinical outcome. However, the frequency of common somatic genomic events occurring in HGSCs from demographically...

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Autores principales:	Paulina M Wojnarowicz, Kathleen Klein Oros, Michael C J Quinn, Suzanna L Arcand, Karen Gambaro, Jason Madore, Ashley H Birch, Manon de Ladurantaye, Kurosh Rahimi, Diane M Provencher, Anne-Marie Mes-Masson, Celia M T Greenwood, Patricia N Tonin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9467faaf430c4f4db00a32587a331be2
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spelling	oai:doaj.org-article:9467faaf430c4f4db00a32587a331be22021-11-18T07:04:45ZThe genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.1932-620310.1371/journal.pone.0045484https://doaj.org/article/9467faaf430c4f4db00a32587a331be22012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23029043/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203High-grade ovarian serous carcinomas (HGSC) are characterized by TP53 mutations and non-random patterns of chromosomal anomalies, where the nature of the TP53 mutation may correlate with clinical outcome. However, the frequency of common somatic genomic events occurring in HGSCs from demographically defined populations has not been explored. Whole genome SNP array, and TP53 mutation, gene and protein expression analyses were assessed in 87 confirmed HGSC samples with clinical correlates from French Canadians, a population exhibiting strong founder effects, and results were compared with independent reports describing similar analyses from unselected populations. TP53 mutations were identified in 91% of HGSCs. Anomalies observed in more than 50% of TP53 mutation-positive HGSCs involved gains of 3q, 8q and 20q, and losses of 4q, 5q, 6q, 8p, 13q, 16q, 17p, 17q, 22q and Xp. Nearly 400 regions of non-overlapping amplification or deletion were identified, where 178 amplifications and 98 deletions involved known genes. The subgroup expressing mutant p53 protein exhibited significantly prolonged overall and disease-free survival as compared with the p53 protein null subgroup. Interestingly, a comparative analysis of genomic landscapes revealed a significant enrichment of gains involving 1q, 8q, and 12p intervals in the subgroup expressing mutant p53 protein as compared with the p53 protein null subgroup. Although the findings show that the frequency of TP53 mutations and the genomic landscapes observed in French Canadian samples were similar to those reported for samples from unselected populations, there were differences in the magnitude of global gains/losses of specific chromosomal arms and in the spectrum of amplifications and deletions involving focal regions in individual samples. The findings from our comparative genomic analyses also support the notion that there may be biological differences between HGSCs that could be related to the nature of the TP53 mutation.Paulina M WojnarowiczKathleen Klein OrosMichael C J QuinnSuzanna L ArcandKaren GambaroJason MadoreAshley H BirchManon de LadurantayeKurosh RahimiDiane M ProvencherAnne-Marie Mes-MassonCelia M T GreenwoodPatricia N ToninPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45484 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paulina M Wojnarowicz Kathleen Klein Oros Michael C J Quinn Suzanna L Arcand Karen Gambaro Jason Madore Ashley H Birch Manon de Ladurantaye Kurosh Rahimi Diane M Provencher Anne-Marie Mes-Masson Celia M T Greenwood Patricia N Tonin The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
description	High-grade ovarian serous carcinomas (HGSC) are characterized by TP53 mutations and non-random patterns of chromosomal anomalies, where the nature of the TP53 mutation may correlate with clinical outcome. However, the frequency of common somatic genomic events occurring in HGSCs from demographically defined populations has not been explored. Whole genome SNP array, and TP53 mutation, gene and protein expression analyses were assessed in 87 confirmed HGSC samples with clinical correlates from French Canadians, a population exhibiting strong founder effects, and results were compared with independent reports describing similar analyses from unselected populations. TP53 mutations were identified in 91% of HGSCs. Anomalies observed in more than 50% of TP53 mutation-positive HGSCs involved gains of 3q, 8q and 20q, and losses of 4q, 5q, 6q, 8p, 13q, 16q, 17p, 17q, 22q and Xp. Nearly 400 regions of non-overlapping amplification or deletion were identified, where 178 amplifications and 98 deletions involved known genes. The subgroup expressing mutant p53 protein exhibited significantly prolonged overall and disease-free survival as compared with the p53 protein null subgroup. Interestingly, a comparative analysis of genomic landscapes revealed a significant enrichment of gains involving 1q, 8q, and 12p intervals in the subgroup expressing mutant p53 protein as compared with the p53 protein null subgroup. Although the findings show that the frequency of TP53 mutations and the genomic landscapes observed in French Canadian samples were similar to those reported for samples from unselected populations, there were differences in the magnitude of global gains/losses of specific chromosomal arms and in the spectrum of amplifications and deletions involving focal regions in individual samples. The findings from our comparative genomic analyses also support the notion that there may be biological differences between HGSCs that could be related to the nature of the TP53 mutation.
format	article
author	Paulina M Wojnarowicz Kathleen Klein Oros Michael C J Quinn Suzanna L Arcand Karen Gambaro Jason Madore Ashley H Birch Manon de Ladurantaye Kurosh Rahimi Diane M Provencher Anne-Marie Mes-Masson Celia M T Greenwood Patricia N Tonin
author_facet	Paulina M Wojnarowicz Kathleen Klein Oros Michael C J Quinn Suzanna L Arcand Karen Gambaro Jason Madore Ashley H Birch Manon de Ladurantaye Kurosh Rahimi Diane M Provencher Anne-Marie Mes-Masson Celia M T Greenwood Patricia N Tonin
author_sort	Paulina M Wojnarowicz
title	The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
title_short	The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
title_full	The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
title_fullStr	The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
title_full_unstemmed	The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
title_sort	genomic landscape of tp53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9467faaf430c4f4db00a32587a331be2
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The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.

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