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. 2021 Oct 29;13(21):5436.
doi: 10.3390/cancers13215436.

Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas

Miriam Gutiérrez-Jimeno  1 , Piedad Alba-Pavón  2 , Itziar Astigarraga  2   3 , Teresa Imízcoz  4 , Elena Panizo-Morgado  1 , Susana García-Obregón  2 , Ana Catalán-Lambán  1 , Mikel San-Julián  5 , José M Lamo-Espinosa  5 , Aizpea Echebarria-Barona  2   3 , Marta Zalacain  1   6 , Marta M Alonso  1   6 , Ana Patiño-García  1   6
Affiliations

Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas

Miriam Gutiérrez-Jimeno et al. Cancers (Basel). .

Abstract

Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing's sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.

Keywords: NGS; genomics; pediatric sarcomas; personalized medicine; targeted therapy.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Genetic alterations detected in our cohort of sarcomas (in order of frequency). Genetic alterations, SNVs, indels, and fusions with a frequency ≥7% or three samples. Altered genes identified in two or fewer sarcoma samples were: ABL2, ACVR1, ARID1A, ARID1B, ASXL1, ATRX, CCND1, CDK4, CDK6, CHD7, CIC, DICER1, ERBB3, FGFR3, GLI1, JAK1, JAK2, IDH1, IGF1R, KDM6A, MET, MYCN, NF1, NF2, NOTCH1, PHF6, PIK3CA, SUZ12, SMARCA4, TCF3, TSC2, WT1, and rearrangements involving AGK-BRAF, ARID1B-MIR-4466, BCOR-CCNB3, EGFR-EGFR, ETV6-NTRK3, EWSR1-CREB1, FGFR2-KIAA1217, FUS-DDIT3, HMGA2-LPP, KMT2C-PRKAG2, NAB2-STAT6, RUNX1-MRPS6, SFPQ-EPS15, SS18-SSX2, SS18-SSX4, TMEM178B-BRAF, ZFP36-FOSB, and ZC3HAV1-BRAF.
Figure 2
Figure 2
Frequent copy number alterations (CNAs).
Figure 3
Figure 3
Fusion genes detected, as depicted in circos plots showing 5′ (blue) and 3′ (orange) fusion genes.
Figure 4
Figure 4
Most frequent genetic alterations in osteosarcoma patients. Genetic alterations, SNVs, indels, and fusions with a frequency ≥11% or two samples. Altered genes identified in less than two sarcoma samples were: ERBB3, GLI1, CDK4, NOTCH1, KDM6A, ASXL1, SMARCA4, DICER1, SMARCB1, CDK6, IGF1R, NF2, TCF3, CDKN2B, ABL2, ARID1B, ARID1A, and rearrangements involving FGFR-KIAA1217, HMGA-LPP, KMT2C-PRKAG2, and SFPQ-EPS15.
See this image and copyright information in PMC

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