Revisiting multiple erroneous genetic testing results and clinical misinterpretations in a patient with Li-Fraumeni syndrome: lessons for translational medicine.
Breast cancer
Li-Fraumeni syndrome
Lung cancer
TP53
Journal
Hereditary cancer in clinical practice
ISSN: 1731-2302
Titre abrégé: Hered Cancer Clin Pract
Pays: Poland
ID NLM: 101231179
Informations de publication
Date de publication:
06 Jan 2021
06 Jan 2021
Historique:
received:
24
06
2020
accepted:
03
12
2020
entrez:
7
1
2021
pubmed:
8
1
2021
medline:
8
1
2021
Statut:
epublish
Résumé
Many cancer patients undergo sophisticated laboratory testing, which requires proper interpretation and interaction between different specialists. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Many cancer patients undergo sophisticated laboratory testing, which requires proper interpretation and interaction between different specialists.
CASE PRESENTATION
METHODS
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
CONCLUSIONS
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.
Identifiants
pubmed: 33407806
doi: 10.1186/s13053-020-00157-8
pii: 10.1186/s13053-020-00157-8
pmc: PMC7789132
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2Subventions
Organisme : Russian Science Foundation
ID : grant 17-75-30027
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