Brain tumors from lung cancer show distinct genetic patterns by subtype
Researchers mapped genetic mutations in brain metastases across different lung cancer types, revealing that tumors spreading to the brain develop unique molecular signatures depending on their origin. The findings could help oncologists predict which patients face brain spread and design targeted treatments—a critical gap since brain metastases remain difficult to treat and reduce survival rates significantly.
Originaltitel: Mutational landscapes of brain metastases across various histological subtypes of lung cancer
<p>The knowledge of the genetic landscape of lung cancer brain metastases (BM) is scarce due to the low availability of intracranial samples. Here, we investigated the genetic features of 142 BM by next-generation sequencing in various lung cancer histological subtypes (19 small-cell lung cancer (SCLC), 123 from non-small-cell lung cancer (NSCLC) including 79 lung adenocarcinomas (LUAD), 31 squamous carcinomas (LUSC), and 13 large-cell lung carcinomas (LCLC). <em>TP53</em>, <em>H3F3A</em>, and <em>PMS2</em> genes were mutated in over 20% of BM, irrespective of their primary histology. LUAD-BM harbored a broad repertoire of mutated proto-oncogenes with tyrosine kinase activity and was significantly associated with APOBEC enrichment and <em>PTEN</em>, <em>EGFR</em>, and <em>NF1</em> gene mutations. <em>TP53</em> and <em>RB1</em> were the most frequently mutated suppressor genes in SCLC-BM. Gene Ontology analysis indicated that SCLC-BM and LCLC-BM were associated with deregulated glial proliferation processes. These findings provide a comprehensive genomic characterization of BM from various lung cancer histologies.</p>