Abstract 1003: Cascade genetic testing for hereditary cancer syndromes in Algerian population: pathways to precision medicine
Authors: Farid Cherbal, Chiraz Mehemmai, Mouchira Saadi, Djamel-Eddine Seddik, Hassen Mahfouf, Wassila Benbrahim, Mohammed Oukkal
Journal: Cancer Research (2025)

Background: Cascade genetic testing helps to identify at risk relatives within hereditary cancer syndromes families with a known germline pathogenic variant in cancer predisposition genes (CPG). The detection of high-risk germline CPG variants in index cases and relatives makes available cancer prevention and precision medicine, respectively. To date, in Algeria, there is a limited access in clinical genetic services, mainly due to the costs and the availability of genetic testing. Here, we report cascade genetic testing in at risk relatives within hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS) and familial adenomatous polyposis syndrome (FAP) families, respectively. Material and Methods: Our study included 7 HBOC families, 4 LS families and 3 FAP families. We screened 34 high risk relatives using PCR-Sanger sequencing for the following CPG germline pathogenic variants: c.181T&amp;gt;G, c.798_799delTT, c.2125-2126insA, c.5332+ 1G&amp;gt;A in BRCA1 gene, c.1310_1313delAAGA, c.8940delA in BRCA2gene, c.1546C&amp;gt;T in MLH1 gene, c.1605dupA, c.2544dupA and c.3584delT in APC gene, respectively. Results: We detected BRCA1 c.181T&amp;gt;G in the brother of the index case. BRCA1 c.798_799delTT has been detected in the sister of the index case. BRCA1 c.2125_2126insA has been detected in two unrelated families and it has been identified in 4 relatives in the first family and 4 relatives in the second family, respectively. In the first family, the sister, the father, the paternal aunt and her son have been tested positive for the variant. The father and the cousin of the index case were disease free. In the second family, the father, the paternal aunt and two brothers of the index case have been tested positive for the variant and were disease free. BRCA1 c.5332+1G&amp;gt;A has been detected in 2 relatives. BRCA2 c.1310_1313delAAGA has been detected in the sister and the father of the proband, while BRCA2 c.8940delA has been identified in the mother and the sister of the proband. Interestingly, the mother was disease free at age 78 years in this family. For LS, MLH1 c.1546C&amp;gt;T detected in 3 related families has been identified in 9 relatives in the first family, 2 relatives in the second family and 3 relatives in the third family. In the third family, MLH1 c.1546C&amp;gt;T has been detected in both parents (mother and father) and in one brother. Interestingly, in this family, a young female sister (not tested) developed glioblastoma and died at age 4 years. As obligate carrier, we can conclude that the young sister developed a CMMRD syndrome. In regard to FAP syndrome, APC c.1605dupA has been detected in 3 sisters and one brother of the proband, APC c.2544dupA has been detected in one relative and APC c.3784delT has been identified in two relatives, respectively. Conclusion: Cascade genetic testing in Algerian population will help to implement strategies to reduce the risk of cancer in families, promote public health and precision medicine. Citation Format: Farid Cherbal, Chiraz Mehemmai, Mouchira Saadi, Djamel-Eddine Seddik, Hassen Mahfouf, Wassila Benbrahim, Mohammed Oukkal. Cascade genetic testing for hereditary cancer syndromes in Algerian population: pathways to precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1003.