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At NSGC, Panelists Tackle Overlap Between Risky Cancer, Prenatal, Pediatric Genes

PITTSBURGH (GenomeWeb) – The worlds of cancer risk testing and prenatal and/or pediatric genetic testing may not be as far apart as they may seem, attendees heard at the annual National Society of Genetic Counselors Education Conference here this week.

During an educational session yesterday afternoon, a panel of experts discussed several scenarios in which counselors may have to make difficult choices about interpreting potential cancer risk information for a parent-to-be based on the detection of certain pediatric syndrome-associated gene variants during prenatal testing.

Conversely, risky variants in some cancer-related genes passed down by parents may combine and get inherited in the couple's offspring in the form of autosomal recessive pediatric syndromes, Kara Maxwell, a hematology and oncology researcher at the University of Pennsylvania's Perelman School of Medicine, explained during her presentation.

In particular, Maxwell pointed to mismatch repair genes such as MLH1, MSH2, MSH6, or PMS2, or DNA repair genes such as BRCA2, PALB2, ATM, or NBN, which may contain cancer-related alterations in adults, but also have documented or more tenuous ties to pediatric syndromes.

That can lead to cases in which prenatal genetics experts have to contend with trying to tease apart potential cancer risks for heterozygous parents based on gene patterns identified during fetal testing — a challenge magnified by the unclear understanding of the cancer risk associated with certain genes or alterations in them.

Similarly, Children's Hospital of Philadelphia genetic counselor Holly Dubbs noted that there have been cases of Fanconi anemia pinned on BRCA2 mutations. As part of her presentation during the panel, Dubbs touched on ways that pediatric testing and/or newborn screening issues can impact parents.

For cancer geneticists, meanwhile, it may become necessary to consider how an adult patient's cancer-associated risk variants could affect his or her chance of having a child affected by a genetic syndrome, despite limited information on how to estimate the precise nature of this risk.

Depending on the nature of a cancer risk variant detected in an adult individual, the risk of pediatric disease in their descendants is often expected to be quite rare, the panelists cautioned.

Still, the possibility raises a host of interpretation and communication challenges, including instances where genetic counselors may have to try to determine risk even when allele frequency or penetrance data isn't available.

Among the questions raised during panel, for example, the panelists discussed the need for more guidelines for determining when that risk warrants discussion with patients, who may already be dealing with new cancer risk information or preparing for the arrival of a child.

The University of Pennsylvania's Amanda Brandt offered an example of the sorts of dilemmas that can come up, presenting a clinical case involving a 62-year-old woman who had lived with ovarian cancer for a dozen years and had an adult daughter who was considering starting a family.

For her part, Kaylene Ready, director of inherited cancer at Counsyl, highlighted the unanticipated information that may arise as expanded carrier screening becomes more widespread, spanning hundreds of genes in individuals of many different ancestral backgrounds.

She explained that such expanded screening is producing new challenges in the way that consent is obtained, the level of evidence needed to implicate a variant in disease risk, the timing and method by which results are returned to parents, and the time when it may be necessary to refer a parent to a cancer geneticist based on newborn screening information.