Abstract 4261: Genomic landscape of 2128 thyroid cancers from the aacr genie database: Implications for targeted therapies

Abstract

Abstract Background: Understanding molecular biology of thyroid cancer has revolutionized diagnosis, tumor classifications and identifying effective precision oncology therapies. Methods: Using AACR GENIE database v.12, we cataloged genetic and co-occurring alterations in all thyroid cancers. Results: We identified 2128 cases from 153,834 samples where tumor sub-histologies included Papillary Thyroid Cancer (PTC: 55%; 1162), Poorly Differentiated Thyroid Cancer (PDTC: 12%; 262); Medullary Thyroid Cancer (MTC: 12%; 244), Anaplastic Thyroid Cancer (ATC: 10%; 220); Follicular Thyroid Cancer (FTC: 5%; 111); Hurthle Cell Thyroid Cancer (HCTC: 5%; 95); and others (1; 34). Median age at sequencing was 59 years. Gender distribution was higher in female (54%; n=1104) compared to male (46%; n=933). Ethnicities included 73.2% (n=1,493) White, 8.9% (n=178) Asian, and others.Most frequent genomic mutational alterations overall were BRAF (40.8%; 868) [96% (n=845) V600E, 0.6% (n=5) G469A, 0.6% (n=5) V600_K601delinsE, 0.2% (n=2) K601E, 0.2% (n=2) A404Cfs*9, and 2.7% (n=24) others]; TERT (35%; 624); NRAS (11.6%; 247); TP53 (11.6%; 247) and RET (9.3%; 197) genes. There was variability in genomic alterations between sub-histologies (Table 1). There was statistically significant co-occurrence between BRAF and TERT, TERT and TP53, TERT and NRAS alterations (p<0.001). Mutually exclusive alterations were BRAF and NRAS, BRAF and RET, TERT and RET, NRAS and RET, TP53 and RET, and BRAF and TP53 (p<0.001).Copy number alterations (CNA) were observed in 497 samples and were most frequent in CDKN2A, NKX2-1, CDKN2B, NF2, and CRKL genes (16.5%, 16%, 15.5%, 13.1%, and 13%). 362 oncogenic fusions were noted predominantly in CCDC6-RET, RET-NCOA4, ETV6-NTRK3, BRAF-Intragenic (20%, 7.2%, 3%, 1.6%). Conclusion: Genomic profiling identified full breadth of BRAF, RET and NRAS alterations and co-occurring oncogenic driver alterations. This approach may refine use of targeted therapy in thyroid cancer. Table 1. Histology Most frequent Alterations % n PTC BRAF 62.3% 724 TERT 32.7% 332 PDTC TERT 49% 117 NRAS 28.2% 74 MTC RET 71.3% 174 HRAS 7.8% 19 ATC TP53 58.2% 128 TERT 56.7% 106 FTC TERT 41% 27 NRAS 26.1% 29 HCTC TERT 41% 34 TP53 17.9% 17 Citation Format: Blessie Elizabeth Nelson, Mohammed Gouda, Jason Roszik, Mimi L. Hu, Maria Cabanillas, Vivek Subbiah. Genomic landscape of 2128 thyroid cancers from the aacr genie database: Implications for targeted therapies. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4261.