Next-Generation Sequencing-based genomic profiling of brain metastases of primary ovarian cancer identifies high number of BRCA-mutations

Journal of Neuro-oncology
S BalendranMatthias Preusser

Abstract

Ovarian cancer represents the most common gynaecological malignancy and has the highest mortality of all female reproductive cancers. It has a rare predilection to develop brain metastases (BM). In this study, we evaluated the mutational profile of ovarian cancer metastases through Next-Generation Sequencing (NGS) with the aim of identifying potential clinically actionable genetic alterations with options for small molecule targeted therapy. Library preparation was conducted using Illumina TruSight Rapid Capture Kit in combination with a cancer specific enrichment kit covering 94 genes. BRCA-mutations were confirmed by using TruSeq Custom Amplicon Low Input Kit in combination with a custom-designed BRCA gene panel. In our cohort all eight sequenced BM samples exhibited a multitude of variant alterations, each with unique molecular profiles. The 37 identified variants were distributed over 22 cancer-related genes (23.4%). The number of mutated genes per sample ranged from 3 to 7 with a median of 4.5. The most commonly altered genes were BRCA1/2, TP53, and ATM. In total, 7 out of 8 samples revealed either a BRCA1 or a BRCA2 pathogenic mutation. Furthermore, all eight BM samples showed mutations in at least one DNA repair gene. Ou...Continue Reading

References

Jun 1, 1989·Gynecologic Oncology·J R Hardy, V J Harvey
Jul 1, 1981·British Journal of Obstetrics and Gynaecology·G H BarkerE Wiltshaw
Dec 2, 2000·Nature·B B Zhou, S J Elledge
Apr 12, 2001·Journal of Clinical Epidemiology·R Bender, S Lange
Dec 18, 2007·Molecular Cell·J Wade Harper, Stephen J Elledge
Dec 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Alan F Rubin, Phil Green
Jul 24, 2010·The American Journal of Pathology·Ernst Lengyel
Apr 7, 2011·Nature Reviews. Clinical Oncology·Martin D ForsterL Rhoda Molife
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Nov 8, 2014·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Houman NafisiJulia Lee Keith
Apr 8, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L BeltrameS Marchini
Jul 15, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Matthias PreusserPeter Birner
Nov 21, 2015·Neoplasia : an International Journal for Oncology Research·Lisa K MullanyJoAnne S Richards
Mar 11, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·U A MatulonisR L Coleman
Apr 3, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MoschettaS Banerjee
May 4, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M A Bookman
May 11, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elena I PentsovaMichael F Berger
May 28, 2016·Gynecologic Oncology Research and Practice·Robert S Meehan, Alice P Chen
Jul 28, 2016·Cancer Biology & Medicine·Robert L Hollis, Charlie Gourley
Oct 30, 2016·European Urology·Joaquin MateoJohann S de Bono
Oct 9, 2016·The New England Journal of Medicine·Mansoor R MirzaUNKNOWN ENGOT-OV16/NOVA Investigators
Nov 12, 2016·Virus Research·Daniel C Anacker, Cary A Moody

❮ Previous
Next ❯

Citations

Sep 25, 2018·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Ji-Woong KwonHo-Shin Gwak
Dec 7, 2019·BMC Cancer·Alexandre André Balieiro Anastácio da CostaGlauco Baiocchi
Oct 2, 2020·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Lawrence KashermanAmit M Oza
Oct 11, 2017·Frontiers in Oncology·Catherine H Han, Priscilla K Brastianos

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
biopsies

Software Mentioned

BaseSpace BWA Enrichment
BWA Genome Alignment
Illumina
Illumina VariantStudio
GATK

Related Concepts

Related Feeds

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Cancer Sequencing

Several sequencing approaches are employed to understand and examine tumor development and progression. These include whole genome as well as RNA sequencing. Here is the latest research on cancer sequencing.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.