51. Probable hereditary familial overlap syndrome with multiple synchronous lung tumors
- Author
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Alejandro Ruiz-Patiño, Luisa Ricaurte, Alberto Balaguera, Leonardo Rojas, Luis Corrales, Adriana Serna, Constanza Navarrete, Zyanya Lucia Zatarain-Barrón, Oscar Arrieta, Juan Carlos Garzón, Rodolfo Barrios, Stella I. Martínez, Cladelis Rubio, and Andrés F. Cardona
- Subjects
Adult ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Cancer Research ,Lung Neoplasms ,Class I Phosphatidylinositol 3-Kinases ,Acinar adenocarcinoma ,Adenocarcinoma ,medicine.disease_cause ,Germline ,CDH1 ,Li-Fraumeni Syndrome ,Neoplasms, Multiple Primary ,Proto-Oncogene Proteins p21(ras) ,Young Adult ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Antigens, CD ,medicine ,Humans ,Lung cancer ,neoplasms ,biology ,business.industry ,High-Throughput Nucleotide Sequencing ,Overlap syndrome ,Cadherins ,medicine.disease ,ErbB Receptors ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Cancer research ,Osteosarcoma ,Female ,KRAS ,business - Abstract
Here we report a case of a young, never-smoker Hispanic woman with a hereditary familial overlap syndrome (Li-Fraumeni plus CDH1). The patient developed multiple synchronous primary lung adenocarcinomas related to Intra-Alveolar Tumor Spread (STAS) several years after the diagnosis of a locally advanced lower limb osteosarcoma. Comprehensive genomic profiling by next generation sequencing (NGS) was performed on 90 cancer-related genes over each lung lesion (including two nodules of acinar adenocarcinoma, one lepidic spread tumor and in the STAS area). Likewise, the broad genomic analysis was performed on archival tissue from the previous bone tumor. Lung tumors were found to harbor PIK3CA (invasive lesions) and a rare in-frame insertion of nucleotides in exon 19 of EGFR (lepidic tumor). STAS area showed KRAS and BRAF mutations in two different segments, and osteosarcoma tested positive for well known PIK3CA, KRAS and CDH1 alterations. This unique case raises practical questions as to the challenges of molecular testing and highlights the potential association of germline TP53 and CDH1 mutations with concurrent somatic alterations that elucidate the basis of tumor heterogeneity.
- Published
- 2018