Prevalence of germline TP53 mutation among early onset middle eastern breast cancer patients

Hereditary Cancer in Clinical Practice

Dahish Ajarim¹  Asma Tulbah²  Fouad Al-Dayel²  Abdul Khalid Siraj³  Maha Al-Rasheed³  Sandeep Kumar Parvathareddy³  Kaleem Iqbal³  Rong Bu³  Tariq Masoodi³  Saud Azam³  Khawla Sami Al-Kuraya⁴ 

[1] Department of Oncology, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, 11211, Riyadh, Saudi Arabia;Department of Pathology, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, 11211, Riyadh, Saudi Arabia;Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, 11211, Riyadh, Saudi Arabia;Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, 11211, Riyadh, Saudi Arabia;Research Center, Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, MBC#98-16, 11211, Riyadh, Saudi Arabia;

关键词: TP53 ;    Breast cancer;    Li-Fraumeni syndrome;    Lifetime risk;   

DOI  :  10.1186/s13053-021-00206-w

来源: Springer

【 摘 要 】

BackgroundThe data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited.MethodsWe determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing.ResultsGermline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS.ConclusionsTP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.

【 授权许可】

CC BY