Probable hereditary familial overlap syndrome with multiple synchronous lung tumors. (October 2018)

• Record Type: Journal Article
• Authors: Cardona, Andrés F.; Zatarain-Barrón, Zyanya Lucia; Rubio, Cladelis; Martínez, Stella; Ruiz-Patiño, Alejandro; Ricaurte, Luisa; Serna, Adriana; Barrios, Rodolfo; Garzón, Juan Carlos; Navarrete, Constanza; Balaguera, Alberto; Corrales, Luis; Rojas, Leonardo; Arrieta, Oscar
• Is Part Of: Lung cancer. Volume 124(2018)
• Page Start: 279
• Page End: 282
• Publication Date: 2018-10
• Subjects: Li fraumeni -- Lung cancer -- Osteosarcoma -- Familial cancer syndrome; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.08.022
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Patient with previous osteosarcoma presented with multiple primary lung tumors. Previous bone, and lung lesions were genotyped by NGS for 90 cancer-related genes. Osteosarcoma tested positive for PIK3CA KRAS and CDH1 alterations (alts). Lung tumors harbored PIK3CA and a rare in-frame insertion in EGFR (exon 19). Potential association of germline ( TP53, CDH1 ) alts with concurrent somatic alts. 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.