RESUMEN
Introduction: Oncogenic mutations in the epidermal growth factor receptor (EGFR) occur frequently in patients with lung cancer. These mutations may serve as critical predictive biomarkers in patients with non-small cell lung cancer (NSCLC). Among them, EGFR exon 18-25 kinase domain duplication (EGFR-KDD) mutations have been identified as a novel EGFR gene subtype in NSCLC. Case Presentation: We reported a rare case of a 59-year-old male diagnosed with adenocarcinoma. A biopsy revealed an EGFR-KDD identified by the next generation sequencing (NGS). Effective treatment outcome has been observed after administration with afatinib. Conclusion: This case highlights that comprehensive NGS technique is valuable in detecting novel genetic mutations in tumors.
RESUMEN
To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation.