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.

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.

Genetic Counseling Clinic at AIIMS (New Delhi).

The field of genetic counseling in India has enormously transformed over the past few years. Genetic counseling is a communication process which deals with the human problems associated with the occurrence or risk of occurrence of a genetic disorder in a family. Genetic counseling is not merely having a conversation based on genomic data. It addresses the "information needs" of a particular patient, and customizes a session according to each patient's individual circumstances, thereby aiding in decision-making. In 2012, AIIMS (New Delhi) became the first tertiary care center in North India to provide genetic counseling for cancer. Among 200 cases that were referred for genetic counseling to the AIIMS clinic at the Department of Surgical Disciplines, about 30% of patients chose to undergo testing. Five cases of BRCA1/2 mutation were found conforming to the hereditary breast and ovarian cancer syndrome. There was one case of TP53 mutation conforming to Li-Fraumeni syndrome. One case each of Xeroderma Pigmentosum (XP) and Cowden's syndrome was also detected. All these cases were offered risk-reducing measures and put under life-long surveillance as per protocol. Their family members were also offered genetic counseling and subsequent testing if they agreed. Cancer genetic counseling service was a new exercise, and hence, several challenges were faced. The clinical utility of genetic testing, coupled with counseling, should be established by trials. Documenting the achievements of counseling by surrogate parameters like "improved recruitment rate of patients for genetic tests" and "improved patient satisfaction levels" will go a long way in garnering the much needed institutional support.