“It is important to note that a paper on managing individuals with germline variants in PALB2 was published in the same issue of Genetics in Medicine as an article on reporting secondary findings in clinical exome and genome sequencing,”1,2 Douglas R. Stewart, MD, told The ASCO Post. “PALB2 is a new addition to that list of findings,” he added. A coauthor of both papers, Dr. Stewart is Senior Investigator, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, at the National Cancer Institute.
“The secondary findings list,” Dr. Stewart explained, “is a well-known resource originally published in 2013. It is a list of medically actionable genes that are unrelated to an indication that someone may be tested for, but if a risk variant is found in those genes, that information should be returned to the physician and the patient. For example, if someone comes in for exome testing because of cardiomyopathy, and as part of that testing, a variant in BRCA1 or BRCA2 is found. Because it is on the secondary findings list, that variant result would be returned to the individual, even though that person didn’t come in for a cancer indication.”
The list includes 73 genes. “Our expectation is that because PALB2 is now on the secondary findings list, many more people will have variants found when exome testing is done for other indications,” Dr. Stewart said. “We expect to get a lot more people identified with a risk variant who may or may not have a family history of breast cancer or ovarian cancer.”
DISCLOSURE: Dr. Stewart performs contract clinical telehealth services for Genome Medical, Inc, in accordance with relevant NCI ethics policies.
1. Tischkowitz M, Balmaña J, Foulkes WD, et al: Management of individuals with germline variants in PALB2. Genet Med 23:1416-1423, 2021.
2. Miller DT, Lee K, Gordon AS, et al: Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med 23:1391-1398, 2021.
PALB2 germline pathogenic variants are associated with a substantially increased risk for breast cancer and a smaller increased risk for pancreatic and ovarian cancers, warranting enhanced surveillance and the option of risk-reducing interventions, according to a global team of cancer genetic...