Abstract 5790: Genomic landscape of circulating tumor DNA alterations in patients with paraganglioma and pheochromocytoma
Authors: Khalil Lana , Tsai Jill , Drusbosky Leylah , Alese Olatunji , Diab Maria , Akce Mehmet , Wu Christina , Gbolahan Olumide Babjide , El-Rayes Bassel , Shaib Walid 
Published: June 2022

Background: Paragangliomas (PGLs) and Pheochromocytomas (PCCs) are rare neuroendocrine tumors (NETs). PGLs arise from chromaffin cells in the ganglia of the autonomic nervous system, while PCCs arise from chromaffin cells in the adrenal medulla. The genomic landscapes of PGLs and PCCs have not been well studied. Thus, the aim of this study is to report differences of mutational occurrences and confirm the feasibility of next generation sequencing (NGS) testing circulating tumor DNA (ctDNA) in patients with PGL and PCC.

Patients and Methods: Molecular alterations in 46 plasma samples were evaluated using a commercially available ctDNA assay (Guardant360® or Guardant360® CDx) across multiple institutions from 2016-2021. The tests detect single nucleotide variants and indels in 54-83 genes with copy number amplifications and fusions in selected genes.

Results: Of the 24 PGL patients, there was a median age of 55 (range:28-78) years and 14 (58%) patients were male. Of the 22 PCC patients, there was a median age of 56 (range:28-86) years and 12 (54.5%) patients were male. Genetic alterations were identified in 16 (67%) PGL and 17 (77%) PCC patients. Of the 16 PGL samples with alterations, TP53 associated genes were most commonly altered (44%), followed by ATM (25%), FGFR2 (19%), APC (13%), BRAF (13%), BRCA1 (13%), CCND2 (13%), FGFR3 (13%), IDH2 (13%), KRAS (13%), PDGFRA (13%), RB1 (13%), TERT(13%), ALK (6%), ARID1A (6%), BRCA2 (6%), CCND1 (6%), CDK6 (6%), CDK12 (6%), EGFR (6%), FGFR1 (6%), KIT (6%), MET (6%), NF1 (6%), NRAS (6%), PIK3CA (6%), PTEN (6%), and ROS1 (6%). Of the 17 PCC samples with alterations, TP53 was most commonly altered (41%), followed by ATM (35%), NF1 (24%), FGFR1 (18%), APC (13%), EGFR (12%), MET (12%), MYC (12%), NOTCH1 (12%), PDGFRA (12%), TSC1 (12%), AR (6%), ARID1A(13%), BRAF (6%), BRCA1 (6%), BRCA2 (6%), CCND1 (6%), CDK6 (6%), CHEK2 (6%), ERBB2 (6%), EZH2 (6%), FGFR2 (6%), IDH2 (6%), KIT (6%), KRAS (6%), NRAS (6%), NTRK1 (6%), NTRK2 (6%), and VHL (6%). 21% of PGL and 41% of PCC patients reported alterations associated with therapies approved in other indications including genes in the MAPK pathway and the homologous recombination repair pathway.

Conclusions: Liquid biopsy is a non-invasive method that can provide personalized treatment options for patients. In this study, we found that evaluation of ctDNA was feasible among individuals with advanced PGL and PCC. We report a high rate of homologous recombinant deficiencies that are in need of evaluation in future Percentage refers to frequency of patients with an alteration detected.

Citation Format: Lana Khalil, Jill Tsai, Leylah Drusbosky, Olatunji Alese, Maria Diab, Mehmet Akce, Christina Wu, Olumide Babjide Gbolahan, Bassel El-Rayes, Walid Shaib. Genomic landscape of circulating tumor DNA alterations in patients with paraganglioma and pheochromocytoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5790.