Abstract 191: Functional role of chromosome 1q loci on breast cancer progression

Abstract Several studies have identified differential expression at various loci on the long arm of chromosome 1 (1q) as the most frequent cytogenetic abnormalities associated with human breast carcinoma. To investigate the impact of genetic alterations on chromosome 1q, we analyzed data from over thirteen thousand human breast tumors (n=13, 146 samples; corresponding to 12, 229 patients across 30 studies) using cBioPortal, which included comprehensive datasets like The Cancer Genome Atlas(TCGA). Our findings revealed that eight genes exhibit significant copy number alterations (12-15%), predominantly amplifications. These genes include TRIM67 (1q42.2, 14%), DISC1 (1q42.2, 14%), REN (1q32.1, 15%), DNM3 (1q24.3, 12%), ATP1B1 (1q24.2, 12%), VSIG8 (1q23.2, 14%), SPTA1 (1q23.1, 14%) and MUC1 (1q22, 14%). In contrast, analysis across more than 100, 000 samples from over 35 different cancers (n=105, 424samples; 101, 597 patients across 226 studies) showed that these genes have much lower alteration frequencies, approximately 3%. Besides, these genes also exhibited notably low expression levels at both RNA and protein levels in normal breast tissues. We further explored the clinical relevance of these genes, examining their roles in breast cancer prognosis and survival outcomes. Our mutual exclusivity and co-occurrence analyses revealed distinct patterns of genetic interplay, indicating a probable collective gain-of-function that drives breast cancer progression. Specifically, TP53 was found to co-occur with MUC1, SPTA1, and VSIG8, while REN exhibited mutual exclusivity. The driver gene PIK3CA co-occurred with DISC1, TRIM67, and REN, whereas ERBB2 showed co-occurrence with all eight genes. These findings suggest a complex network of genetic interactions that may underlie invasive and metastatic breast cancer phenotypes. Additionally, we observed that some of the above mentioned gene products (proteins) including REN (Renin) are detectable in serum, suggesting potential as biomarkers for recurrence or prognosis. Our ongoing studies are focused on validating these proteins as diagnostic and therapeutic targets. Collectively, this study underscores the importance of multi-locus evaluation on chromosome 1q, which could pave the way for novel diagnostic and therapeutic strategies in breast cancer management. Citation Format: Alakesh Bera, Eric Russ, Hai Hu, Craig D. Shriver, Meera Srivastava. Functional role of chromosome 1q loci on breast cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 191.