Germline TP53 mutations is common in patients with two early‐onset primary malignancies

Clinical Outcomes of TP53 Mutations in Cancers

“…Recently, testing recommendations have been broadened to include women with early-onset breast cancer in the absence of family history or BRCA1/ BRCA2 mutations (McCuaig et al 2012), as they would be suspected of carrying de novo TP53 germline mutations (Gonzalez et al 2009). In addition, germline TP53 mutations have now been uncovered in patients who did not fulfill the clinical criteria for LFS testing, but presented with rare pediatric cancers including hypodiploid acute lymphoblastic leukemia (Holmfeldt et al 2013), melanoma (Lu et al 2015), gastric adenocarcinoma (Chang et al 2013), early-onset colorectal cancer (Yurgelun et al 2015), early-onset osteosarcoma (Mirabello et al 2015), or multiple early-onset malignancies (Yamada et al 2009;Chak et al 2015). The wide application of NGS technologies will undoubtedly lead to more such findings and require continued reassessment of the role of TP53 germline variants in cancer predisposition and the need for intense surveillance of mutation carriers and their families (Villani et al 2011).…”

A Case of Male Primary Pulmonary Choriocarcinoma

“…This variant has been reported in ovary, lung, central nervous system, and hematopoietic cancers. [5] Experimental studies have shown that this missense change disrupts the transcriptional transactivation function of the TP53 protein. This finding suggests that the aspartic acid residue may be critical for TP53 protein function and that missense substitutions at this position may be pathogenic and may contribute to the development of choriocarcinoma.…”