NOTCH1

This study characterized the genomic landscape of leiomyosarcoma, a rare and aggressive tumor, by analyzing a large dataset from the AACR Project GENIE. Researchers examined over 1,000 tumor samples, identifying the most frequent somatic mutations and copy number alterations. TP53, RB1, and ATRX were the most commonly altered genes, with homozygous deletions of RB1 and TP53, and MAP2K4 amplifications. The study also highlighted enriched IGF2 and AXIN1 alterations in metastatic samples, suggesting their potential role in disease progression. These findings enhance the understanding of leiomyosarcoma biology and could guide future precision oncology strategies.

This retrospective study investigated the frequency and molecular profiles of PAX8-positive conventional urothelial carcinomas (UCs) of the urinary bladder. Out of 101 cases, 10% were found to be PAX8-positive by immunohistochemistry. Next-generation sequencing (NGS) was performed on 20 cases, including all PAX8-positive UCs. The findings revealed that PAX8-positive UCs frequently harbored TERT promoter mutations, TSC1 alterations, NOTCH1 loss, and WT1 loss, while notably lacking RB1 loss, distinguishing them from PAX8-negative UCs. These results indicate a distinct molecular signature for PAX8-positive UCs, emphasizing the need for careful diagnostic interpretation of PAX8.

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.