Ultrasensitive Detection of Chromosomal Instability in Ascites as a Novel Diagnostic for Peritoneal Carcinomatosis

Background Diagnosing peritoneal carcinomatosis (PC) remains challenging. This study aims to evaluate the value of ascites chromosomal instability (CIN) analysis in the diagnosis of PC. Methods We performed low-coverage whole-genome sequencing on 50 human ascites samples. CIN was profiled using ultrasensitive chromosomal aneuploidy detection (UCAD), and its diagnostic performance was validated against pathological standards. Results CIN analysis detected peritoneal metastases with 90.0% sensitivity and 82.0% overall accuracy. In malignant ascites, 72.7% were CIN-positive, showing recurrent alterations (e.g., 3q gain, 14q loss) that formed co-occurring gain/loss modules. Unsupervised clustering identified three CIN subtypes with distinct genomic instability patterns. Conclusion Ascites CIN analysis shows promise as a highly sensitive, minimally invasive diagnostic tool for PC. The identified CIN patterns and subtypes provide insights into peritoneal metastasis biology and hold promise for clinical stratification.