title: Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India.
abstract: Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories, ⩽40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes.
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Ashraf U
authors.initials: AU
authors.lastname: Mannan
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Jaya
authors.initials: J
authors.lastname: Singh
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Ravikiran
authors.initials: R
authors.lastname: Lakshmikeshava
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Nishita
authors.initials: N
authors.lastname: Thota
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Suhasini
authors.initials: S
authors.lastname: Singh
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: T S
authors.initials: TS
authors.lastname: Sowmya
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Avshesh
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Shivani
authors.initials: S
authors.lastname: Deshwal
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Megha R
authors.initials: MR
authors.lastname: Soni
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Anbukayalvizhi
authors.initials: A
authors.lastname: Chandrasekar
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Ramesh
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Bharat
authors.initials: B
authors.lastname: Ramamurthy
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Shila
authors.initials: S
authors.lastname: Padhi
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Payal
authors.initials: P
authors.lastname: Manek
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Ramalingam
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: Triesta Sciences, Health Care Global Enterprises Limited, Bangalore, India.
authors.forename: Mithua
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Sankaran
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Arunabha
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Vamsi
authors.initials: V
authors.lastname: Veeramachaneni
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.|Department of Medicine, Division of Bioinformatics and Personalized Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Preveen
authors.initials: P
authors.lastname: Ramamoorthy
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.|Department of Computer Science and Automation, Indian Institute of Science, Bangalore, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Hariharan
authors.affiliation: Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
authors.forename: Kalyanasundaram
authors.initials: K
authors.lastname: Subramanian
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing / Q000379:methods; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007194:India / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015995:Prevalence; D055815:Young Adult