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Germline mutations of the adenomatous polyposis coli (APC) gene in Algerian familial adenomatous polyposis cohort: first report

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Abstract

Background

Familial adenomatous polyposis (known also as classical or severe FAP) is a rare autosomal dominant colorectal cancer predisposition syndrome, characterized by the presence of hundreds to thousands of adenomatous polyps in the colon and rectum from an early age. In the absence of prophylactic surgery, colorectal cancer (CRC) is the inevitable consequence of FAP. The vast majority of FAP is caused by germline mutations in the adenomatous polyposis coli (APC) tumor suppressor gene (5q21). To date, most of the germline mutations in classical FAP result in truncation of the APC protein and 60% are mainly located within exon 15.

Material and methods

In this first nationwide study, we investigated the clinical and genetic features of 52 unrelated Algerian FAP families. We screened by PCR-direct sequencing the entire exon 15 of APC gene in 50 families and two families have been analyzed by NGS using a cancer panel of 30 hereditary cancer genes.

Results

Among 52 FAP index cases, 36 had 100 or more than 100 polyps, 37 had strong family history of FAP, 5 developed desmoids tumors, 15 had extra colonic manifestations and 21 had colorectal cancer. We detected 13 distinct germline mutations in 17 FAP families. Interestingly, 4 novel APC germline pathogenic variants never described before have been identified in our study.

Conclusions

The accumulating knowledge about the prevalence and nature of APC variants in Algerian population will contribute in the near future to the implementation of genetic testing and counseling for FAP patients.

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Data availability

Data that support the conclusions of this article are included within the article.

Abbreviations

APC :

Adenomatous polyposis coli gene

CRC:

Colorectal cancer

CHRPE:

Congenital hypertrophy of the retinal pigment epithelium

FAP:

Familial adenomatous polyposis syndrome

LGR:

Large genomic rearrangement

MLPA:

Multiplex ligation probe amplification

NGS:

Next generation sequencing

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Acknowledgements

We deeply thank the patients and their families for their participation. This study was supported by the Algerian National Research Program FNRSDT (D01N01UN160420130007) and PRFU (Project N° D01N01UN160420180005). Farid Cherbal would like to deeply and warmly thank Dr Alicia Zhou and Color Genomics (Burlingame, California, United States, https://www.color.com) for performing the NGS analysis in our Algerian FAP patients using Hereditary Cancer Test. Farid Cherbal would like to thank Imene Tabet, Sihem Hamine, Fatma Narimane Nouredine, Sarah Sabri and Adam Walid Damache for their big help with the FAP patients and cancer data. Farid Cherbal would like to thank Dr Philippe Maillet (Ornex, France), Prof. Kada Boualga (Anti Cancer Center, Blida, Algeria), Daoud Cherbal (Paris, France) and Romaissa Cherbal (Paris, France) for their permanent support to the research program on hereditary cancers in Algerian population.

Funding

The funded was provided by FNRSDT, (Grant No: D01N01UN160420130007). PRFU, (Grant No D01N01UN160420180005).

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Authors and Affiliations

  1. Molecular Genetics Team, LMCB, Faculty of Biological Sciences, FBS, University of Science and Technology Houari Boumediene, El–Alia, Bab-Ezzouar, POB 32, 16111, Algiers, Algeria

    Feriel Khider, Farid Cherbal & Asma-Lamia Boumehdi

  2. Gastroenterology Service, School of Medicine, University Hospital Mustapha Bacha, Algiers, University of Algiers-1, Algiers, Algeria

    Karim Layaida

  3. School of Medicine, Mohamed El Kolli Public Hospital, Academic Medical Oncology Services, University of Algiers-1, Rouiba, Algeria

    Hassen Mahfouf

  4. School of Medicine, Mohamed El Kolli Public Hospital, Academic General Surgery Services, University of Algiers-1, Rouiba, Algeria

    Ferhat Zebboudj

  5. School of Medicine, Bachir Mentouri Public Hospital, Academic General Surgery Services, University of Algiers-1, Kouba, Algiers, Algeria

    Mustapha Maaoui

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  1. Feriel Khider
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Contributions

FK collected and selected the FAP families, carried out the molecular genetics studies, analysis and interpretation of data, funding acquisition (Doctoral fellowship). FC prepared the study concept and design, supervised the study, participated in FAP families’ recruitment, carried out the molecular genetics studies, did the sequence alignment, data analysis and interpretation, funding acquisition, writing, drafting, reviewing and revising the manuscript. ALB participated in FAP families’ recruitment, analysis and interpretation of data. KL, HM, FZ and MM contributed to data collection and clinical data analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Farid Cherbal.

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Conflict of interest

The authors declare non conflict of interest.

Ethical approval

All patients, relatives and parents/legally authorized representatives of the minor subjects tested for APC germline mutations and screened by PCR-direct sequencing and NGS analysis, respectively, signed written informed consent. The study was approved by the institutional review boards and ethical approval was obtained from appropriate institutions (USTHB, EPH Mohamed El Kolli, EPH Bachir Mentouri, University Hospital Mustapha Bacha, FNRSDT D01N01UN160420130007 and PRFU D01N01UN160420180005, 61 participants, start date: 3/1/2012, end date: 5/8/2019).

Informed consent

Informed consent was obtained from all individual participants and from parents/legally authorized representatives of the minor subjects included in the study.

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This study has been presented (in part) in a poster session at the 68th Annual Meeting of the American Society of Human Genetics (ASHG), 18 October 2018 in San Diego, California, USA.

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Khider, F., Cherbal, F., Boumehdi, AL. et al. Germline mutations of the adenomatous polyposis coli (APC) gene in Algerian familial adenomatous polyposis cohort: first report. Mol Biol Rep 49, 3823–3837 (2022). https://doi.org/10.1007/s11033-022-07228-0

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