Abstract C057: Whole-exome sequencing of DNA from Palestinian women undergoing surgical evaluation for breast cancer

Abstract

Background: A Palestinian woman with breast cancer only has 50% chance of being alive at five years. Lack of access to medical care is further complicated by political strife, checkpoints, and the need to file a permit for traveling even a short distance. Preliminary studies of Palestinian women under 40 with breast cancer show a low frequency of BRCA1/BRCA2 mutations. These studies suggest that there may be unique genetic, epigenetic, and environmental drivers of aggressive cancers in Palestinian women. Here we have developed the Palestinian infrastructure to start to investigate these drivers. We report our efforts to build infrastructure and our initial findings. Methods: To build capacity, we first trained 2 Palestinians in genetic counseling using the City of Hope Distance Learning Program. We engaged a group of Palestinian breast surgeons from the cities of Ramallah, Jerusalem, Nabulus, and Hebron. Together we built the infrastructure for blood and tissue collection/preservation. Our protocol was first approved by the Palestinian Ministry of Health and Palestinian Helsinki Committee. To date we have enrolled 65 Palestinian women from throughout Palestine and collected matched breast cancer tissue and matched white blood cells (WBC) DNA. On WBC DNA we performed whole-exome sequencing (WES) to search for germline mutations. Exomes were enriched using Agilent SureSelectHumanAllExonV6+COSMIC V2 kit, which covers 66 MB of the genome. Any deleterious mutation will be formally verified by MyriadTM United States CAP-CLIA-approved testing. Results: The average age of the 65 women was 44 (range 18-78). Women were tested for mutations in 20 genes known to be associated with DNA repair and breast cancer. Of these 65 women, none had a family history of breast cancer; to date, no known pathogenic variants have been identified in these women. Parallel studies in a second group of Palestinian women with a history of familial breast cancer had pathogenic mutations in 11 different genes: BRCA1, BRCA2, TP53, ATM, CHEK2, BARD1, BRIP1, PALB2, MRE11A, PTEN and XRCC2. The single most frequent mutation was TP53 p.R181C, which was significantly enriched in the discovery series compared to controls (p50.01) and was responsible for 15% of breast cancers among young onset or familial patients. Conclusions: The genetic and possibly epigenetic origins of breast cancer in Palestinian women may be distinct from non-Hispanic White Women. We have formed a Palestinian Coalition to ethically obtain matched WBC and tumor tissue from Palestinian women with breast cancer. Our studies show that in accordance with Helsinki Principles, we have developed the infrastructure to return testing results to the referring physicians. Note: This abstract was not presented at the conference. Citation Format: Sundus Shalabi, Jerneja Tomsic, NourAl-Huda Hamad, Susan Neuhausen, Osama Atallah, Saeed Mustafa, Akram AbuHeibeh, Omar Abdul-Shafi, Nufuz Maslamani, Bashar Karmi, Ola Abu-Kishik, Jehad Shawar, Haifa Aqeilan, Aya Awad, Rami Aqeilan, Ahmad Dalbah, Hanood Abras, Abdul-Rahman Salamheh, Firas Jallad, Hisham Darwish, Victoria Seewaldt. Whole-exome sequencing of DNA from Palestinian women undergoing surgical evaluation for breast cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C057.