Researchers have understood for decades the importance that DNA repair mechanisms play in maintaining genomic integrity and keeping carcinogenesis in check. For instance, the BRACA1/2 genes and protein products have been found to play a critical role in the development and outcome of breast and ovarian cancers. So important are these two genes that they become an integral part of breast and ovarian cancer diagnostics. Yet, a recent international survey of genetic testing labs shows that global protocols and standards are surprisingly inconsistent when it comes to analyzing these cancer susceptibility genes and their many variations.       

A multi-institutional team led investigators at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC–James) published their findings recently in npj Genomic Medicine, in an article entitled “Clinical Testing of BRCA1 and BRCA2: A Worldwide Snapshot of Technological Practices.” The researchers surveyed 86 genetic testing laboratories around the world to better understand their testing practices for BRCA1/2, known cancer susceptibility genes linked to the types of breast and ovarian cancer passed down through families.

“Clinical testing of BRCA1 and BRCA2 began over 20 years ago. With the expiration and overturning of the BRCA patents, limitations on which laboratories could offer commercial testing were lifted,” the authors wrote. “These legal changes occurred approximately the same time as the widespread adoption of massively parallel sequencing (MPS) technologies. Little is known about how these changes impacted laboratory practices for detecting genetic alterations in hereditary breast and ovarian cancer genes. Therefore, we sought to examine current laboratory genetic testing practices for BRCA1/BRCA2.”

The vast majority of responding labs—93%—used modern next-generation sequencing technologies that allow for simultaneous screening of multiple genes in a single, advanced test. Just six relied on Sanger sequencing methods, the traditional approach used for genetic testing prior to the availability of advanced genomic testing tools like next-generation sequencing.

Overall, the researchers found that laboratories differed widely in their approach to analyzing BRCA—including in the extent of variant confirmation, whether noncoding DNA regions were sequenced, and the techniques used to detect large genomic rearrangements that could provide clues about future cancer risk.

“We employed an online survey of 65 questions covering four areas: laboratory characteristics, details on technological methods, variant classification, and client-support information,” the authors noted. “Eight United States (US) laboratories and 78 non-US laboratories completed the survey. Most laboratories (93%; 80/86) used MPS platforms to identify variants. Laboratories differed widely on: (1) technologies used for large rearrangement detection; (2) criteria for minimum read depths; (3) non-coding regions sequenced; (4) variant classification criteria and approaches; (5) testing volume ranging from 2 to 2.5 × 105 tests annually; and (6) deposition of variants into public databases.”

“This is important because it means that patients could be getting a different level of accuracy in their genetic results, based on the level of testing beyond baseline BRCA1/2 testing—there are variants of these cancer susceptibility genes that could be missed by some approaches and which are important to know about in terms of overall cancer risk,” concluded lead study investigator Amanda Toland, Ph.D., assistant professor at The Ohio State University Comprehensive Cancer Center. “Global best-practice guidelines for BRCA testing are needed to ensure consistency in testing for patients, regardless of where they obtain their testing.”  


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