Lana Khalil, Ali F. Al Sbihi, Jill Tsai, Leylah M Drusbosky, Hiba I Dada, Bassel El-Rayes and Walid Shaib*
Background: Paragangliomas (PGLs) and Pheochromocytomas (PCCs) are rare cancers. There is not standard of care treatments for these cancers. The genomic landscape of PGLs and PCCs is not reported. The aim of this study is to report the mutational difference and assess the feasibility of Next Generation Sequencing (NGS) testing by Circulating Tumor DNA (ctDNA) from patients with PGLs and PCCs.
Methods: Molecular alterations in 46 plasma samples were tested using Guardant360® or Guardant360® CDx ctDNA assays from multiple institutions 2016-2021. Single nucleotide variants and indels in 54-83 genes with copy number amplifications and fusions in selected genes were detected.
Results: A total of 46 patients (24 PGLs and 22 PCCs) were included. For the 24 PGLs patients, the median age was 55 (range: 28-78); 14 (58%) were male. Of the 22 PCCs patients, the median age was 56 (range: 28-86); 12 (54.5%) were male. The identified genetic alterations were present in 16 (67%) PGLs and 17 (77%) PCCs patients. The 16 PGLs mutations include: TP53 (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%). The 17 PCCs alterations include: TP53 (41%), followed by ATM (35%), NF1 (24%), FGFR1 (18%), APC (13%), EGFR (12%), MET (12%), MYC (12%), NOTCH (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%).
Conclusion: Liquid biopsy was feasible to detect alterations in PGLs and PCCs patients. ctDNA is a non-invasive method with the ability to detect alterations that could help personalize the treatment options for patients. We report a high rate of Homologous Recombinant Deficiencies (HRD) among the PGLs/PCCs patients highlighting the need for prospective evaluation on clinical trials.
Published Date: 2024-08-30; Received Date: 2024-07-31
