Background Many cancer patients undergo sophisticated laboratory testing, which requires proper interpretation and interaction between different specialists. Case presentation We describe a patient with an extensive family history of cancer, who was diagnosed with bilateral breast cancer and two lung cancer lumps by the age of 40 years. She submitted a lung cancer specimen to a genetic profiling service, which reported the presence of the EGFR mutation (a combination of G719S and L833V substitutions) and the TP53 с.322_327del (p.G108_F109del) mutation in the tumor tissue. Possible therapeutic options were discussed at a medical conference, where one of the discussants raised a concern that the identified TP53 mutation may not necessarily be somatic, but reflect the germ-line status of the gene. Review of clinical records and follow-up dialog with the patient revealed, that she previously provided her blood for DNA analysis in two laboratories. The first laboratory utilized a custom NGS assay and did not detect the TP53 mutation, instead pointed to a potential pathogenic significance of the MSH6 c.2633 T > C (p.V878A) allele. The second laboratory revealed the TP53 с.322_327del (p.G108_F109del) allele but stated in the written report that it has an unknown pathogenic significance. To resolve the possible uncertainty regarding the role of the TP53 с.322_327del (p.G108_F109del) variant, we suggested that the patient invite her second cousin for genetic testing, as she was affected by neuroblastoma at the age of 3 years. This analysis revealed the presence of the same TP53 variant. Conclusion We provide point-by-point discussion, reviewing multiple laboratory mistakes and clinical misinterpretations occurred with this patient. This case report exemplifies the need to involve rigorous clinical expertise in the daily practice of medical laboratory facilities.

中文翻译：

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重新审视 Li-Fraumeni 综合征患者的多个错误基因检测结果和临床误解：转化医学的经验教训

背景 许多癌症患者接受复杂的实验室检查，这需要不同专家之间的正确解释和互动。病例介绍 我们描述了一名具有广泛癌症家族史的患者，他在 40 岁时被诊断出患有双侧乳腺癌和两个肺癌肿块。她将肺癌标本提交给基因分析服务，该服务报告肿瘤组织中存在 EGFR 突变（G719S 和 L833V 替代的组合）和 TP53 с.322_327del（p.G108_F109del）突变。在一次医学会议上讨论了可能的治疗选择，其中一位讨论者提出了一个担忧，即已识别的 TP53 突变可能不一定是体细胞的，而是反映了基因的种系状态。回顾临床记录和与患者的后续对话显示，她之前曾在两个实验室提供血液用于 DNA 分析。第一个实验室使用定制的 NGS 检测并没有检测到 TP53 突变，而是指出 MSH6 c.2633 T > C (p.V878A) 等位基因的潜在致病意义。第二个实验室揭示了 TP53 с.322_327del (p.G108_F109del) 等位基因，但在书面报告中指出它具有未知的致病意义。为了解决关于 TP53 с.322_327del (p.G108_F109del) 变体作用的可能不确定性，我们建议患者邀请她的第二个堂兄进行基因检测，因为她在 3 岁时患有神经母细胞瘤。该分析揭示了相同的 TP53 变体的存在。结论 我们提供逐点讨论，回顾了该患者发生的多个实验室错误和临床误解。本病例报告说明了在医学实验室设施的日常实践中需要严格的临床专业知识。