Abstract 5055: Efficient detection of chromosomal instability in diverse cancers using a targeted sequencing approach
Authors: Hua Bao, Rui Liu, Haimeng Tang, Ningyou Li, Min Wu, Xunbiao Liu, Zhili Chang, Xue Wu
Journal: Cancer Research (2025)

Abstract Objective: Chromosomal instability (CIN), characterized by frequent chromosomal alterations, plays a crucial role in tumorigenesis, significantly influencing cancer progression and therapeutic resistance. Targeting vulnerabilities associated with CIN, particularly in DNA repair pathways, presents promising therapeutic strategies. However, existing CIN detection methods are often costly and labor-intensive. Thus, the development of efficient and cost-effective CIN detection panels is essential for optimizing cancer treatments and enhancing patient outcomes while reducing healthcare costs. Methods: We conducted a retrospective study analyzing 4, 941 tissue samples from patients diagnosed with 14 distinct cancer types, including ovarian, uterine, breast, pancreatic, prostate, cervical, liver, lung, colorectal, and gastric cancers. A targeted sequencing panel, GENESEEQ GENAVISTA, assessing 437 cancer-associated genes with an approximate depth of coverage of 1, 000X, facilitated detailed mutational profiling. CIN assessment utilized read depth and allele frequency evaluation, alongside variant calling algorithms to identify gene duplications and genomic rearrangements. Additionally, a prospective cohort of 33 cancer patients was analyzed to compare the efficacy of our sequencing panel against the gold standard of whole genome sequencing (WGS, ∼30X). Results: Our analysis revealed significant CIN prevalence across various cancer types, particularly elevated in ovarian cancer (73.26%) and breast cancer (76.80%). Lung cancer exhibited a CIN rate of 78.57%, while melanoma demonstrated an 80.00% prevalence. Endometrial cancer presented a moderate CIN rate of 40.62%, whereas pancreatic cancer displayed an equal distribution between CIN and genomically stable tumors, each accounting for 50.00%. Prostate cancer showed a CIN incidence of 45.16%, and cervical cancer recorded a rate of 62.30%. The findings illustrate the heterogeneous nature of CIN among malignancies, suggesting its utility as a prognostic marker and therapeutic target. The panel demonstrated a high correlation with WGS results in the prospective cohort (Spearman rank correlation = 0.91), confirming its effectiveness in identifying CINs in cancer patients. Conclusion: Our study establishes the GENESEEQ GENAVISTA targeted sequencing panel as an effective tool for accurately detecting CIN across various cancer types. The strong correlation with whole genome sequencing highlights its potential as a reliable, cost-effective alternative for CIN assessment, facilitating optimized cancer treatment strategies and improving patient outcomes while minimizing healthcare costs. Citation Format: Hua Bao, Rui Liu, Haimeng Tang, Ningyou Li, Min Wu, Xunbiao Liu, Zhili Chang, Xue Wu. Efficient detection of chromosomal instability in diverse cancers using a targeted sequencing approach [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 5055.