Abstract 655: Clinicopathological and genetic features of colorectal cancer in Algerian patients
Authors: Cherbal Farid , Boumehdi Asma Lamia , Khider Feriel , Nouredine Fatma Narimane , Layaida Karim , Mahfouf Hassen , Maaoui Mustapha 
Published: August 2019

Abstract
Background Colorectal carcinoma is the third most common form of cancer worldwide. It is the second most common cancer in men and women in Algeria.The aim of this study was to determine clinicopathological and genetic features of colorectal cancer in Algerian patients. For the genetic study, we focused on the two major forms of hereditary colorectal cancer, Familial Adenomatous Polyposis (FAP) and Lynch Syndrome (LS), respectively.
Materials and Methods The study population included 366 patients diagnosed with colorectal cancer (CRC). Colorectal carcinoma was diagnosed between January 2017 to March 2018. Clinical and tumor data: age at diagnosis, site of tumor and TNM stage were collected from the medical records of the patients. We screened by PCR-direct sequencing exon 15 of APC gene in 30 patients with a strong family history of classic FAP. 30 patients with Lynch syndrome who fulfilled Amsterdam criteria were screened by PCR- direct sequencing for germline mutations in the MMR genes: MLH1 (exons 9,10,13,16), MSH2 (exons 5,6,7,12) and MSH6 (exon 4). Two FAP patients and two LS patients were screened by NGS using a cancer panel of 30 hereditary cancer genes (Color Genomics, California, USA).
Results In this retrospective study, there were 183 women (50%) and 183 men (50%).The median age at diagnosis cancer was 58 years old. The highest proportions of CRC were observed for the age groups 60-69, 50-59 and 40-49 years, 25.4%, 23.49%, 20.49% respectively. We noticed that colorectal tumors were not uniformly distributed through the large bowel. Rectum was the most common site (26.8%) followed by right colon (20.5%), sigmoid colon (18.9%) left colon (13.7%) and caecum (7.4%). Our results showed that 75.95% of the CRC patients were diagnosed at TNM stage II (9.02%), stage III (48.63%) and stage IV (18.31%), respectively. The analysis of DNA samples of FAP patients revealed that 6 patients carried pathogenic variants in APC gene. 3 distinct pathogenic variants: c.1605dupT ( one patient), c.3784delT (2 related patients), and c.3927_3931delAAAGA (3 unrelated patients) were identified in APC gene. Moreover, three distinct germline mutations: c.55_63delATCGCGGCGinsT in exon 1 of MLH1 (one patient), c.1165C&gt;T in exon 7 of MSH2 ( one patient) and the Newfoundland mutation c.942 +3A&gt;T in exon 5 of MSH2 (3 unrelated patients) were detected in 5 Lynch syndrome families.The APC c.1605dupT and c.3784delT and the MLH1 c.55_63delATCGCGGCGinsT new variants have never been reported in LOVD, UMD and ClinVar databases and could be specific of Algerian FAP patients and Lynch syndrome patients, respectively. Haplotype analysis of the APC c.3927_3931delAAAGA and the c.942+3A&gt;T MSH2 variants will establish their genetic origin in Algeria.
Conclusions The accumulative knowledge about clinicopathological and genetic characteristics of colorectal cancer in Algerian patients will impact on clinical management in the areas of both prevention and treatment.
Citation Format: Farid Cherbal, Asma Lamia Boumehdi, Feriel Khider, Fatma Narimane Nouredine, Karim Layaida, Hassen Mahfouf, Mustapha Maaoui. Clinicopathological and genetic features of colorectal cancer in Algerian patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 655.