

Submission Type:Original Research Article
1 aboratory of Medical Genetics, Ibn Rochd University Hospital, Casablanca,
2 Laboratory of Cellular and Molecular Pathology, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University
3 aboratory of Medical Genetics, Ibn Rochd University Hospital, Casablanca
High-throughput next-generation sequencing has revolutionized cancer molecular diagnosis and research. Indeed, molecular analysis revealed that the same type of tumor may exhibit diverse molecular subgroups. This technology enables the identification of novel specific genes implicated in tumor progression. Moreover, identification of specific mutations and active molecular pathways play a crucial role in identifying new drug targets. The present study highlights the clinical utility of next-generation sequencing in the management of cancer by reporting three patients with family cancer history (Li-Fraumeni syndrome, breast cancer, and colon cancer), observed in the Medical Genetics Department of Ibn Rochd University Hospital in Casablanca, Morocco.
Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): A population-based study. Lancet Oncol. 2012;13(8):790–801. https://doi.org/10.1016/S1470-2045(12)70211-5
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. https://doi.org/10.1016/j.cell.2011.02.013
Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009;458(7239):719–24. https://doi.org/10.1038/nature07943
Pon JR, Marra MA. Driver and passenger mutations in cancer. Annu Rev Pathol. 2015;10:25–50. https://doi.org/10.1146/annurev-pathol-012414-040312
McFarland CD, Korolev KS, Kryukov GV, Sunyaev SR, Mirny LA. Impact of deleterious passenger mutations on cancer progression. Proc Natl Acad Sci U S A. 2013;110(8):2910–5. https://doi.org/10.1073/pnas.1213968110
Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4(1):36–54. https://doi.org/10.3978/j.issn.2218-6751.2014.05.01
Bedard PL, Hansen AR, Ratain MJ, Siu LL. Tumour heterogeneity in the clinic. Nature. 2013;501(7467):355–64. https://doi.org/10.1038/nature12627
Jacob A. Apport du séquençage d’exome pour le diagnostic et le traitement des maladies complexes. Médecine humaine et pathologie. Lille; 2020.
Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010;11(10):685–96. https://doi.org/10.1038/nrg2841
Ilić MP, Kiralj A, Markov B, Mijatov I, Mijatov S, Vučković N. Li-Fraumeni syndrome: a case report. Vojnosanit Pregl. 2014;71(12):1159–62. https://doi.org/10.2298/vsp1412159i
Fortuno C, James PA, Spurdle AB. Current review of TP53 pathogenic germline variants in breast cancer patients outside Li-Fraumeni syndrome. Hum Mutat. 2018;39(12):1764–73. https://doi.org/10.1002/humu.23656
Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome. Lancet Oncol. 2011;12(6):559–67. https://doi.org/10.1016/S1470-2045(11)70119-X
Jégu M, Some Der A, Morcel K, Abadie C, Fritel X, Levêque J. Cancers du sein et de l'ovaire liés aux mutations constitutionnelles délétères BRCA1&2 et reproduction. J Gynecol Obstet Biol Reprod. 2015;44(1):10–7. https://doi.org/10.1016/j.jgyn.2014.10.011
Chen J, Bae E, Zhang L, Hughes K, Parmigiani G, Braun D, et al. Penetrance of breast and ovarian cancer in women who carry a BRCA1/2 mutation. JNCI Cancer Spectr. 2020;4(4):pkaa029. https://doi.org/10.1093/jncics/pkaa029
Aissaoui S, Aissaoui H. Le Conseil Génétique en Pathologie Humaine. Paris: Elsevier Masson; 2017.
Kuchenbaecker KB, McGuffog L, Barrowdale D, Lee A, Soucy P, Dennis J, et al. Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2017;109(7):djw302. https://doi.org/10.1093/jnci/djw302
Lee SH, Jung SH, Kim TM, Rhee JK, Park HC, Kim MS, et al. Whole-exome sequencing identified mutational profiles of high-grade colon adenomas. Oncotarget. 2017;8(4):6579–88. https://doi.org/10.18632/oncotarget.14172
Kim TM, Lee SH, Chung YJ. Clinical applications of next-generation sequencing in colorectal cancers. World J Gastroenterol. 2013;19(40):6784–93. https://doi.org/10.3748/wjg.v19.i40.6784
Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–7. https://doi.org/10.1038/nature11252
Brannon AR, Vakiani E, Scott S, Sylvester B, Kania K, Viale A, et al. Targeted next-generation sequencing of colorectal cancer identified metastatic-specific genetic alterations. BMC Proc. 2012;6(Suppl 6):P3. https://doi.org/10.1186/1753-6561-6-S6-P3
Al Bitar S, El-Sabban M, Doughan S, Abou-Kheir W. Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer. World J Gastroenterol. 2023;29(9):1395–426.
Lacoste C, Fabre A, Pécheux C, Lévy N, Krahn M, Malzac P, et al. Le séquençage d’ADN à haut débit en pratique clinique. Arch Pédiatr. 2017;24(4):373–83. https://doi.org/10.1016/j.arcped.2017.01.008
Comité Consultatif National d'Ethique pour les Sciences de la Vie et de la Santé (CCNE). Génétique et médecine : de la prédiction à la prévention. Paris: La Documentation française; 1997