TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution

Al-Qasem,Abeer  J.; Toulimat,Mohamed; Eldali,Abdelmoneim  M.; Tulbah,Asma; Al-Yousef,Nujoud; Al-Daihan,Sooad  K.; Al-Tassan,Nada; Al-Tweigeri,Taher; Aboussekhra,Abdelilah

doi:10.3892/ol.2011.236

TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution

Authors:
- Abeer J. Al-Qasem
- Mohamed Toulimat
- Abdelmoneim M. Eldali
- Asma Tulbah
- Nujoud Al-Yousef
- Sooad K. Al-Daihan
- Nada Al-Tassan
- Taher Al-Tweigeri
- Abdelilah Aboussekhra
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Affiliations: Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center BMR, Riyadh 11211, Saudi Arabia, Department of Pathology, King Faisal Specialist Hospital and Research Center BMR, Riyadh 11211, Saudi Arabia, Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center BMR, Riyadh 11211, Saudi Arabia, Department of Genetics, King Faisal Specialist Hospital and Research Center BMR, Riyadh 11211, Saudi Arabia, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia, Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia
Published online on: January 18, 2011 https://doi.org/10.3892/ol.2011.236
Pages: 363-369

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Abstract

Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4-9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals.

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