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Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient

BACKGROUND: Ovarian carcinoma is a common, and often deadly, gynecological cancer. Mutations in BRCA1 and BRCA2 genes are present in at least a fifth of patients. Uncovering other genes that become mutated subsequent to BRCA1/BRCA2 inactivation during cancer development will be helpful for more effe...

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Autores principales: Zhang, Jian, Shi, Yuhao, Lalonde, Emilie, Li, Lili, Cavallone, Luca, Ferenczy, Alex, Gotlieb, Walter H, Foulkes, William D, Majewski, Jacek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614563/
https://www.ncbi.nlm.nih.gov/pubmed/23522120
http://dx.doi.org/10.1186/1471-2407-13-146
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author Zhang, Jian
Shi, Yuhao
Lalonde, Emilie
Li, Lili
Cavallone, Luca
Ferenczy, Alex
Gotlieb, Walter H
Foulkes, William D
Majewski, Jacek
author_facet Zhang, Jian
Shi, Yuhao
Lalonde, Emilie
Li, Lili
Cavallone, Luca
Ferenczy, Alex
Gotlieb, Walter H
Foulkes, William D
Majewski, Jacek
author_sort Zhang, Jian
collection PubMed
description BACKGROUND: Ovarian carcinoma is a common, and often deadly, gynecological cancer. Mutations in BRCA1 and BRCA2 genes are present in at least a fifth of patients. Uncovering other genes that become mutated subsequent to BRCA1/BRCA2 inactivation during cancer development will be helpful for more effective treatments. METHODS: We performed exome sequencing on the blood, primary tumor, omental metastasis and recurrence following therapy with carboplatin and paclitaxel, from a patient carrying a BRCA1 S1841R mutation. RESULTS: We observed loss of heterozygosity in the BRCA1 mutation in the primary and subsequent tumors, and somatic mutations in the TP53 and NF1 genes were identified, suggesting their role along with BRCA1 driving the tumor development. Notably, we show that exome sequencing is effective in detecting large chromosomal rearrangements such as deletions and amplifications in cancer. We found that a large deletion was present in the three tumors in the regions containing BRCA1, TP53, and NF1 mutations, and an amplification in the regions containing MYC. We did not observe the emergence of any new mutations among tumors from diagnosis to relapse after chemotherapy, suggesting that mutations already present in the primary tumor contributed to metastases and chemotherapy resistance. CONCLUSIONS: Our findings suggest that exome sequencing of matched samples from one patient is a powerful method of detecting somatic mutations and prioritizing their potential role in the development of the disease.
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spelling pubmed-36145632013-04-05 Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient Zhang, Jian Shi, Yuhao Lalonde, Emilie Li, Lili Cavallone, Luca Ferenczy, Alex Gotlieb, Walter H Foulkes, William D Majewski, Jacek BMC Cancer Research Article BACKGROUND: Ovarian carcinoma is a common, and often deadly, gynecological cancer. Mutations in BRCA1 and BRCA2 genes are present in at least a fifth of patients. Uncovering other genes that become mutated subsequent to BRCA1/BRCA2 inactivation during cancer development will be helpful for more effective treatments. METHODS: We performed exome sequencing on the blood, primary tumor, omental metastasis and recurrence following therapy with carboplatin and paclitaxel, from a patient carrying a BRCA1 S1841R mutation. RESULTS: We observed loss of heterozygosity in the BRCA1 mutation in the primary and subsequent tumors, and somatic mutations in the TP53 and NF1 genes were identified, suggesting their role along with BRCA1 driving the tumor development. Notably, we show that exome sequencing is effective in detecting large chromosomal rearrangements such as deletions and amplifications in cancer. We found that a large deletion was present in the three tumors in the regions containing BRCA1, TP53, and NF1 mutations, and an amplification in the regions containing MYC. We did not observe the emergence of any new mutations among tumors from diagnosis to relapse after chemotherapy, suggesting that mutations already present in the primary tumor contributed to metastases and chemotherapy resistance. CONCLUSIONS: Our findings suggest that exome sequencing of matched samples from one patient is a powerful method of detecting somatic mutations and prioritizing their potential role in the development of the disease. BioMed Central 2013-03-22 /pmc/articles/PMC3614563/ /pubmed/23522120 http://dx.doi.org/10.1186/1471-2407-13-146 Text en Copyright © 2013 Zhang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Jian
Shi, Yuhao
Lalonde, Emilie
Li, Lili
Cavallone, Luca
Ferenczy, Alex
Gotlieb, Walter H
Foulkes, William D
Majewski, Jacek
Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient
title Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient
title_full Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient
title_fullStr Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient
title_full_unstemmed Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient
title_short Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient
title_sort exome profiling of primary, metastatic and recurrent ovarian carcinomas in a brca1-positive patient
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614563/
https://www.ncbi.nlm.nih.gov/pubmed/23522120
http://dx.doi.org/10.1186/1471-2407-13-146
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