ATM

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 study assesses the performance of in silico prediction tools for genetic variant curation within a panel of cancer predisposition genes. Researchers applied ClinGen SVI Working Group recommended thresholds and AlphaMissense predictions to variants in genes such as BRCA1, BRCA2, TP53, TERT, and ATM, which have established pathogenicity or benignity. The findings indicated insufficient sensitivity for pathogenic TERT variants and benign TP53 variants. The study emphasizes that the performance of these tools can be gene-specific and is influenced by their training datasets. Consequently, it is crucial to validate these tools for individual genes, especially for missense variants.

Clear cell adenocarcinoma of the urinary tract (CCA-UT) is a rare and aggressive tumor with limited understanding of its clinicopathologic and molecular features. This multi-institutional study characterized 35 cases, showing a female predominance and advanced stage at presentation. Genomic alterations were found in 91% of cases, frequently involving chromatin modifiers such as ATRX, KMT2C, ARID1A, and ARID1B. The heterogeneous molecular profile of these tumors highlights the critical role of molecular analysis in identifying potential therapeutic targets.