Distinct NSCLC Variants in a Family With Li-Fraumeni Syndrome: Case Report.

Introduction: Heritable lung cancer may occur in the context of germline mutations (Li-Fraumeni syndrome). Limited cases of intrafamily tumor genomic characteristics have been reported.

Main Concerns Important Clinical Findings Primary Diagnoses interventions Outcomes: A 40-year-old woman with no smoking history or known environmental exposure risk was incidentally found to have stage II (T2N1) NSCLC harboring an exon 19 p.Glu746_Ala750 deletion. Family history was notable for an identical twin sister with colorectal cancer (diagnosed at age 31 y) and a mother with stage I NSCLC harboring an exon 21 c.2573T>G (p.Leu858Arg) mutation (diagnosed at age 69 y). Genetic testing revealed a germline c.542G>A (p.Arg181His) mutation in the patient, her mother, and her sister, consistent with Li-Fraumeni syndrome. No germline mutations were detected.

Conclusion: Shared germline mutations may be associated with distinct NSCLC somatic mutations within families with Li-Fraumeni syndrome. Further understanding of the association between genetic cancer syndromes and lung cancer risk may improve early lung cancer detection in populations not otherwise meeting screening eligibility.