The advantages of the panel over currently available single-gene tests are described in the 2 March edition of the Journal of Human Genetics. NGS technologies parallelise the sequencing process, producing thousands or millions of sequences concurrently.
Ramesh Hariharan, an author of the study and chief technology officer with the developers, Strand Life Sciences, Bangalore, says that “breast cancer is on the increase, particularly in urban India.” He notes that about 100,000 cases of the disease occur annually in India where patients are typically younger than in Western countries and have a higher incidence of triple-negative breast cancer.
Breast cancer diagnosis is generally based on receptors for estrogen, progesterone and human epidermal growth factor 2 , with treatments targeting these ‘triple negatives’.
“The younger age of onset, the higher proportion of triple negatives, all indicate there just might be a higher incidence of genomic mutations in the Indian population conferring risk,” Hariharan tells SciDev.Net. “This is what we found in our study.” As part of the study, 141 unrelated patients and families with breast or ovarian cancer were tested for mutations in 13 genes associated with high inherited risk using the TruSight panel. More than a third of those cases showed a clear inherited risk, with the figure rising to 52 per cent for cases with a family history of breast cancer.
“Both numbers were higher than expected,” Hariharan says. Most of the results were on account of mutations in the commonly tested BRCA1 and BRCA2 genes. However, Hariharan notes that 28 per cent of the mutations detected were in other genes, and 37 percent had not been reported earlier in patients. The finding indicates a “novel variation in the Indian population” and demonstrates that multigene panels have advantages over single-gene tests favoured by oncologists.
“NGS-based sequencing will clearly help identify people who are at risk early enough so they can increase surveillance or take proactive avoidance measures,” says Hariharan. “It does need a fair amount of awareness that cancers have inherited risk that can be detected early,” he acknowledges.
Manish Singhal, a medical oncologist at Indraprastha Apollo Hospitals, New Delhi, says it is “clear that NGS is the method to test” for heritable risk in cancer patients. At the same time, he encourages caution in using such multigene panels as the information generated could complicate the treatment decision-making process.
“While there is no denying that multigene panels are fast evolving, economical and rapid, the information derived may have many adverse clinical outcomes if done as reflex testing,” says Singhal.
“Clinical relevance would require specialised genetic counselling and understanding of the phenotype before we even order the genotypic testing,” Singhal says. “It should not appear that we intend to sell multigene testing as hotcakes.”
This piece was produced by SciDev.Net’s South Asia desk.