Metb-06. High Frequency of Clinically Relevant Alterations Detected by Integrated Tumor and Germline Gene Panel Testing in Children With Cns Tumors – Results From the Texas Kidscanseq Study
Year: 2023
Type: conference-abstract
Abstract: BACKGROUND Tumor and germline alterations detected by sequencing have the potential to inform management of children with CNS tumors. Comparative clinical utility data for available molecular sequencing modalities are needed to optimize testing strategies. METHODS Cancer patients less than 18 years of age were eligible to enroll in the Texas KidsCanSeq (KCS) clinical genomics study at six Texas institutions. Blood testing was performed on all patients using a pediatric solid tumor targeted DNA panel (124 genes), which included 35 genes associated with known cancer predisposition syndromes. Tumor testing was conducted on high-risk or recurrent tumors using the same DNA panel as well as an 81-gene RNA fusion panel. Tumor variants were classified as being of strong (Tier 1) or potential (Tier 2) clinical significance following AMP/ASCO/CAP guidelines. Germline pathogenic (P) or likely pathogenic (LP) variants per ACMG/AMP guidelines were considered clinically relevant. RESULTS A total of 224 children with CNS tumors were enrolled, including 146 patients with high-risk or recurrent tumors. Tissues were sufficient for analysis from 132 tumors and 211 germline samples. Clinically relevant alterations were identified in 90 of 132 (68%) tumors tested. Of 50 with therapeutic implications, 21 (42%) were not known from prior clinical testing. Therapeutically relevant tumor variants most frequently involved BRAF (n=20), CDKN2A/B (n=16), SMARCB1 (n=9), PIK3CA (n=8), and NF1 (n=7). One high grade glioma (in a patient with Lynch syndrome) was found to be hypermutated (tumor mutation burden >190 mut/Mb). Germline analysis detected P/LP variants in cancer predisposition genes in 25 of 211 (12%) patients tested, including 12 of 135 (9%) with high-risk/recurrent tumors. CONCLUSION Combined tumor and germline panel testing revealed alterations of clinical relevance according to consensus guidelines in approximately 70% of children with high-risk or recurrent CNS tumors.
Source: Neuro-Oncology
Authors: Frank Y Lin, Lauren Desrosiers, Ross Mangum, Jacquelyn Reuther, Carrie Mohila, Melissa M Blessing, Guillermo Aldave, Donna M Muzny, Juan Carlos Bernini, Jonathan Gill, Timothy Griffin, Gail Tomlinson, Kelly Vallance, Murali M Chintagumpala, Sarah Scollon, Dolores H López-Terrada, Kevin E Fisher, Angshumoy Roy, Sharon E Plon, D Williams Parsons
Institutions: Baylor College of Medicine, Phoenix Children's Hospital, Invitae (United States), Texas Children's Hospital, The University of Texas MD Anderson Cancer Center, Children's Hospital of San Antonio, The University of Texas at San Antonio Health Science Center, Cook Children's Medical Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,612
OpenAlex ID: W4380302525