Abstract 1762: Characterization of somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma

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Abstract Deletion in the long arm of chromosome 22 (22qDEL) is the most prevalent somatic copy number alteration (SCNA) observed in papillary thyroid carcinoma (PTC). Despite its recurrence, the specific characteristics and role of 22qDEL in PTC have not been fully studied. We conducted a pooled analysis of 22qDEL by integrating patient and clinical information and molecular profiles from 1,094 primary PTC tumors across four major published PTC genomic studies: The Cancer Genome Atlas (TCGA) PTC profile study, the National Cancer Institute (NCI) post-Chornobyl PTC study, the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSKCC-IMPACT) PTC cases, and the Seoul National University (SNU) thyroid cancer profile study. The majority of PTC with 22qDEL demonstrated arm-level loss of heterozygosity (86%). Even in PTC cases with partial 22qDEL, we observed a loss across 70% of chromosome 22, encompassing regions 22q12 and 22q13, which harbors known cancer genes (NF2 and CHEK2). More than 90% of 22qDEL co-occurred with established oncogenic drivers of PTC, though a full assessment of PTC drivers was not available for all cases. 22qDEL occurred more frequently with RAS point mutations (50.4%) than other drivers (9.3%). A higher fraction of 22qDEL was clonal in RAS-driven PTCs (78.3%), suggesting 22qDEL occurs early in RAS-driven tumor development. We did not observe any association between 22qDEL and established PTC risk factors such as age, sex, and radiation, nor with clinical features including tumor size, multifocality, and metastasis (p-values>0.22). RNA sequencing gene expression analysis based on 22qDEL status revealed downregulation of most genes residing on chromosome 22q and significant differential expression activity of immune-related genes, further implicating a role of immune dysregulation in PTC. Our study suggests that 22qDEL may not act as a primary driver of PTC but plays an important role as a co-factor of RAS point mutations, which could further drive PTC development. Citation Format: Olivia W. Lee, Danielle Karyadi, Stephen Hartley, Weyin Zhou, Mitchell Machiela, Mykola Tronko, Tetiana Bogdanova, Liudmyla Zurnadzhy, Lindsay Morton, Stephen Chanock. Characterization of somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1762.

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