The study identified pathogenic or likely pathogenic variants in known cancer-susceptibility genes in a substantial number of children with sporadic neuroblastoma. These variants were mostly inherited and they correlated with worse outcome.
The findings from the Gabriella Miller Kids First (GMKF) neuroblastoma X01 cohort study were presented during the American Association for Cancer Research (AACR) virtual annual meeting by Dr. Emily Blauel with Children's Hospital of Philadelphia.
"The GMKF neuroblastoma cohort provides a rich and unique dataset that is allowing unanswered questions to be addressed," Dr. Blauel said during a press briefing.
The researchers performed whole-genome sequencing (WGS) of germline DNA from 556 children with neuroblastoma and one or both of their biological parents. Sequencing of matched tumor DNA and RNA was also performed.
The researchers identified 93 pathogenic or likely pathogenic germline variants in known cancer predisposition genes across 90 patients, representing 16% of the cohort.
Sequencing data available from 85 biological parents of these patients found that 94% of the identified germline variants were inherited, with an equal distribution inherited between mothers and fathers.
All pathogenic or likely pathogenic germline variants were identified in tumor DNA.
Having a pathogenic or likely pathogenic germline variant in a cancer-predisposition gene was associated with worse outcomes, including lower odds of 10-year event-free survival (66.9% vs. 79.7%) and 10-year overall survival (76.5% vs. 89.4%), compared with those without such variants.
"The observed associations of pathogenic and likely pathogenic germline variants with worse outcomes suggest that we need a more thorough genetic evaluation of patients with neuroblastoma than is currently performed as standard of care," Dr. Blauel said in an AACR press release.
It's currently estimated that only 1% to 2% of children with neuroblastoma have a family history of the disease, with the remainder of cases are believed to occur sporadically.
"By studying 556 patients and having information from both parents, the investigators have been able document that the heritability of neuroblastoma is probably higher than before, because 16%, or 90 cases all together, had germline variants that were the same in either one of the parents of the affected child suggesting that the neuroblastoma would have been inherited," said AACR president and briefing moderator Dr. Antoni Ribas.
"The patients that had these variants also have worse outcomes. This is very important information because it could allow genetic counseling to these families. It also opens the door for future studies analyzing the function of these genes and how they could we used therapeutically to treat neuroblastoma," said Dr. Ribas.
The study was supported by the National Institutes of Health. The authors have no relevant disclosures.
SOURCE: https://bit.ly/3mFbWXK American Association for Cancer Research virtual annual meeting, held April 10-15, 2021.
By Megan Brooks
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