Open Access Highly Accessed Research article

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

Jian Zhang12, Yuhao Shi12, Emilie Lalonde12, Lili Li13, Luca Cavallone3, Alex Ferenczy4, Walter H Gotlieb56, William D Foulkes136* and Jacek Majewski12

Author Affiliations

1 Department of Human Genetics, McGill University, Montreal, QC, Canada

2 Genome Quebec Innovation Centre, Montreal, QC, Canada

3 Program in Cancer Genetcs, Departments of Oncology and Human Genetics, McGill University, Montreal, QC, Canada

4 Departments of Pathology, McGill University and Jewish General Hospital, 546 Pine Avenue West, Montreal, QC H2W 1S6, Canada

5 Departments of Obstetrics & Gynecology and Oncology, McGill University, Montreal, QC, Canada

6 Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada

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BMC Cancer 2013, 13:146  doi:10.1186/1471-2407-13-146

Published: 22 March 2013



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.


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.


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.


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.

Driver mutations; Gynecological cancer; Hereditary cancer; Next generation sequencing; Tumor suppressor genes; Chromosomal rearrangements