A new Cleveland Clinic study demonstrates the importance of genetics evaluation and genetic testing for children, adolescents and young adults with solid tumour cancers.

The study was published in Nature Communications.

Solid tumours account for half of cancer cases in children, adolescent and young adult (C-AYA) patients.

The majority of these cases are assumed to result from germline variants (heritable changes affecting all cells in the body) rather than somatic alterations.

However, little is known regarding the spectrum, frequency and implications of these germline variants.

In this study, led by Charis Eng, M.D., Ph.D., Cleveland Clinic's Genomic Medicine Institute, the researchers conducted the largest-to-date evaluation of germline mutations in C-AYA patients with solid tumours utilising a combined dataset from Cleveland Clinic and St. Jude Children's Research Hospital.

Of the 1,507 patients analysed, 12% carried germline pathogenic and/or likely pathogenic variants in known cancer-predisposing (KCPG) genes while an additional 61% had germline pathogenic variants in non-KCPG genes.

"Our findings emphasise the necessity for all C-AYA patients with solid tumours to be sent for genetics evaluation and gene testing," said Dr Eng. "Adult guidelines, particularly family history, are typically used to recognise C-AYA patients with possible heritable cancer, but studies have found a family history of cancer in only about 40% of patients with pathogenic and/or likely pathogenic variants."

The researchers also conducted a drug-target network analysis to determine if the pathogenic and/or likely pathogenic germline variants detected in the dataset were located within genes that could potentially be targeted by drug therapies.

Their analysis found that 511 (34%) patients had at least one pathogenic and/or likely pathogenic variant on a gene that is potentially druggable.

Notably, they discovered that approximately one-third of these patients had variants that can be targeted by existing FDA-approved drugs.

"Currently, the majority of available targeted therapies are geared to adult patients, leaving few safe and effective treatment options for C-AYA patients," noted Dr Eng. "However, we found that a significant number of the germline altered genes in C-AYA solid tumour cancers are targetable by FDA-approved drugs, which presents an opportunity to harness drug repurposing to identify therapeutic options for C-AYA patients."

Source: Cleveland Clinic