PMC:6037202 / 42730-44267 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6037202","sourcedb":"PMC","sourceid":"6037202","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6037202","text":"Genes can remain uninvestigated by clinicians not only because of uncertainty surrounding risks but also because of recency of discovery. A number of CPGs in which variants were identified, such as MAX and FH, have been relatively recently described as causing pheochromocytoma and paraganglioma. The appearance of these variants in this analysis most likely reflects a lack of availability of testing at the time of consultation and subsequent referral for inclusion in the study. Molecular genetic testing has been available for other genes such as MLH1 and PTEN for a greater period of time, but some individuals appeared not to have fulfilled the clinical testing criteria applied in the referring center. TP53 is a further well-established CPG that is associated with diverse and multiple cancers and has clear clinical testing criteria that are often not fulfilled. Despite this, no pathogenic variants were detected. Germline TP53-variant-related phenotypes (including rare and/or early-onset cancers) are more clearly identifiable clinically and are less likely to appear in cohorts such as ours without specific ascertainment for them. Consistent with this are mutation detection rates of ∼4% in individuals with earlier-onset (≤30 years) breast cancer36 and ∼17% in MPT-affected individuals who were referred for germline TP53 testing and who generally fulfilled criteria for that investigation, had tumors characteristic of Li Fraumeni syndrome, and had an average age at diagnosis (of a first primary tumor) before 30 years.2","tracks":[{"project":"2_test","denotations":[{"id":"29909963-12672316-2051627","span":{"begin":1261,"end":1263},"obj":"12672316"},{"id":"29909963-19204208-2051628","span":{"begin":1536,"end":1537},"obj":"19204208"}],"attributes":[{"subj":"29909963-12672316-2051627","pred":"source","obj":"2_test"},{"subj":"29909963-19204208-2051628","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93e9","default":true}]}]}}