Cancer of Unknown Primary

This study investigates a simplified approach to identify lung origin in cancers of unknown primary (CUP). Researchers found that the presence of SMARCA4 mutations, combined with a history of smoking, is strongly associated with lung-origin CUP (CUP-Lung). This combination offers a 76% probability of lung origin, even without detectable pulmonary involvement. This method could serve as a surrogate for whole-genome sequencing (WGS) to guide organ-directed treatments.

This study analyzed the genomic profile of 480 patients with metastatic adenocarcinoma of unknown primary (ACUP) using the FoundationOne CDx platform. The most frequent mutations included TP53, KRAS, and CDKN2A. Results showed that GNAS and PIK3CA mutations were associated with better overall survival. Conversely, ARID1A and NOTCH1 alterations were linked to a worse prognosis. These findings highlight the significance of specific genomic alterations as prognostic markers in ACUP.