Incidental findings in genomics | EurekAlert!

Vienna, Austria: As the cost of the genome and exome1 The fall of sequencing, its use in characterizing rare diseases and personalizing cancer treatment, for example, is becoming more frequent. However, such analyzes may lead to results unrelated to the condition for which they were requested. What to do with these secondary outcomes (SFs) or incidental outcomes (IFs) is problematic. Should the patient be informed of it and in what circumstances? How should clinical geneticists deal with the unnecessary anxiety they might cause?

At the annual conference of the European Society of Human Genetics today (Saturday), Ms Estella Carrasco, MSc, PhD student and genetic counselor at Vall d’Hebron Hospital, Barcelona, ​​Spain, will describe how she and her colleagues set out to research. on the prevalence of SF/IFs in cancer susceptibility genes (CSGs) in patients who have undergone exome sequencing due to rare diseases not related to cancer, and to identify CSGs with potential clinical action unrelated to the purpose of the initial analysis. They then assessed the psychological impact of detecting SF/IFs for patients and their relatives compared to a group tested because of their family history of cancer. They analyzed the exomes of 533 patients screened for non-cancerous indications and followed up with the Psychological Impact Screening for detection of SF/IFs for these patients two to six months after the delivery of the results.

“We found pathogenic variants SF/IFs (that may cause disease) in CSGs in 2% of patients who had exome testing for reasons unrelated to cancer predisposition,” Carrasco says. “This enabled us to perform predictive testing on 42 relatives, 18 of whom are CSG carriers.”

Psychological impact was higher in those in which the variant was identified as an incidental outcome, but this needs to be weighed against the advantage of early detection and preventive strategies that can be offered in families who did not have a previous diagnosis of cancer, the researchers say. “Although the rate of 2% of SF/IFs may not seem very high, it is noteworthy. Genetic counseling can help communicate results and help patients and their families adjust to the newly discovered genetic condition,” says Ms. Carrasco.

The researchers intend to continue researching new ways to present genetic test results to patients; For example, the effect of separating the time at which primary outcomes are detected from secondary outcomes. “We believe that the ability to demonstrate clinical feasibility for secondary outcomes is reassuring for patients.”

Of the 29 carriers identified (11 indicator cases and 18 close relatives), 20 were enrolled for further monitoring. Researchers were able to identify three paragangliomas (a type of neuroendocrine tumor) and early breast cancer in a 74-year-old woman with: BRCA2 Variable that terminated population-based breast cancer screening. close one in BRCA2 The family with metastatic prostate cancer was given targeted therapy after it was infected BRCA2 The case has been detected.

However, special problems appear in the case of children. “The principle of child autonomy may be lost if disclosed before an appropriate age, so healthcare professionals should exercise caution when ordering exome sequencing analysis in minors,” says Carrasco. On the other hand, disclosing these findings could generate an indirect benefit for these children as it may allow their relatives to adhere to early detection and prevention programmes, thus preserving their health. To achieve this, it is important to report only clinically actionable genes.

“It is important to provide adequate counseling to individuals undergoing exome sequencing, or in the case of children to their parents or guardians, in order to ensure that they understand all potential medical applications of genetic testing. On a professional level, in cases where exome sequencing is requested by clinicians who have With a little training in communicating information about SF/IFs, genetic counselors and clinical geneticists should form part of the multidisciplinary team providing care.”

Professor Alexandre Raymond, Conference Chair, said: “Unlike radiologists, whose incidental findings suggest a tumor, geneticists’ incidental discoveries are often predictive in nature. While this should not prevent us from acting on an actionable finding, only This requires dedicated and specially trained staff to ensure that all information provided to patients and their families is clear, comprehensible and comprehensible.”

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Abstract C02. 5 Dealing with incidental findings in cancer susceptibility genes after exome sequencing in pediatric patients

1 The exome consists of all the exons in the genome. These are the DNA sequences that code for the protein and are therefore the functional part of the genome.


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