Scientific publications

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing

Feb 20, 2023 | Magazine: Scientific Reports

Piedad Alba-Pavón #  1 , Lide Alaña #  1 , Miriam Gutierrez-Jimeno  2 , Susana García-Obregón  1   3 , Teresa Imízcoz  4 , Elena Panizo  2 , Paula González-Urdiales  1   5 , Aizpea Echebarria-Barona  1   5 , Ricardo Lopez Almaraz  1   5 , Laura Zaldumbide  1   6 , Itziar Astigarraga  1   5   7 , Ana Patiño-García  2   4   8 , Olatz Villate  9


Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes.

The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes. This study included 43 pediatric and young adult patients with different sarcoma subtypes. Tumor profiling was undertaken using the Oncomine Childhood Cancer Research Assay (Thermo Fisher Scientific).

Sequencing results were reviewed for potential germline alterations in clinically relevant genes associated with cancer predisposition syndromes. Jongmans´ criteria were taken into consideration for the patient selection. Fifteen patients were selected as having potential pathogenic germline variants due to tumor sequencing that identified variants in the following genes: CDKN2A, NF1, NF2, RB1, SMARCA4, SMARCB1 and TP53.

The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome.

CITATION  Sci Rep. 2023 Feb 20;13(1):2959.  doi: 10.1038/s41598-023-29982-2

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