Long-read genome and RNA sequencing resolve a pathogenic intronic germline LINE-1 insertion in APC

Rahman, N. Realising the promise of cancer predisposition genes. Nature 505, 302–308 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Groden, J. et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66, 589–600 (1991).

Article  CAS  PubMed  Google Scholar 

Nishisho, I. et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253, 665–669 (1991).

Article  CAS  PubMed  Google Scholar 

Yen, T. et al. APC-Associated Polyposis Conditions. 1998 [Updated 2022]. In: Adam, M. P. et al. (eds) GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025.

Zaffaroni, G. et al. Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision. Br. J. Surg. 111, znae070 (2024).

Article  PubMed  PubMed Central  Google Scholar 

National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Colorectal Version 1.2023. (National Comprehensive Cancer Network, 2023).

Valle, L. & Monahan, K. J. Genetic predisposition to gastrointestinal polyposis: syndromes, tumour features, genetic testing, and clinical management. Lancet Gastroenterol. Hepatol. 9, 68–82 (2024).

Article  CAS  PubMed  Google Scholar 

Grover, S. et al. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA 308, 485–492 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stanich, P. P. et al. Prevalence of germline mutations in polyposis and colorectal cancer–associated genes in patients with multiple colorectal polyps. Clin. Gastroenterol. Hepatol. 17, 2008–2015.e3 (2019).

Article  CAS  PubMed  Google Scholar 

Aretz, S. et al. Large submicroscopic genomic APC deletions are a common cause of typical familial adenomatous polyposis. J. Med. Genet. 42, 185–192 (2005).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rohlin, A. et al. Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis. Oncogene 30, 4977–4989 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chung, C. C. Y. et al. Meta-analysis of the diagnostic and clinical utility of exome and genome sequencing in pediatric and adult patients with rare diseases across diverse populations. Genet. Med. 25, 100896 (2023).

Article  CAS  PubMed  Google Scholar 

Auton, A. et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).

Article  PubMed  Google Scholar 

Huddleston, J. et al. Discovery and genotyping of structural variation from long-read haploid genome sequence data. Genome Res. 27, 677–685 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Beck, C. R., Garcia-Perez, J. L., Badge, R. M. & Moran, J. V. LINE-1 elements in structural variation and disease. Annu. Rev. Genomics Hum. Genet. 12, 187–215 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Deininger, P. Alu elements: know the SINEs. Genome Biol. 12, 236 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dombroski, B. A., Mathias, S. L., Nanthakumar, E., Scott, A. F. & Kazazian, H. H. Isolation of an active human transposable element. Science 254, 1805–1808 (1991).

Article  CAS  PubMed  Google Scholar 

Ostertag, E. M. & Kazazian, H. H. Jr Biology of mammalian L1 retrotransposons. Annu. Rev. Genet. 35, 501–538 (2001).

Article  CAS  PubMed  Google Scholar 

Hancks, D. C. & Kazazian, H. H. Roles for retrotransposon insertions in human disease. Mob. DNA 7, 9 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Vogt, J. et al. SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints. Genome Biol. 15, R80 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Zhou, D. et al. Insertion of LINE-1 Retrotransposon inducing exon inversion causes a rotor syndrome phenotype. Front. Genet. 10, 1–6 (2020).

Belancio, V. P., Roy-Engel, A. M. & Deininger, P. The impact of multiple splice sites in human L1 elements. Gene 411, 38–45 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Van Belzen, I. A. E. M., Schönhuth, A., Kemmeren, P. & Hehir-Kwa, J. Y. Structural variant detection in cancer genomes: computational challenges and perspectives for precision oncology. npj Precis. Onc 5, 1–11 (2021).

Google Scholar 

Sedlazeck, F. J., Lee, H., Darby, C. A. & Schatz, M. C. Piercing the dark matter: bioinformatics of long-range sequencing and mapping. Nat. Rev. Genet. 19, 329–346 (2018).

Article  CAS  PubMed  Google Scholar 

Carvalho, C. M. B. & Lupski, J. R. Mechanisms underlying structural variant formation in genomic disorders. Nat. Rev. Genet 17, 224–238 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Joe, S. et al. Comparison of structural variant callers for massive whole-genome sequence data. BMC Genomics 25, https://doi.org/10.1186/s12864-024-10239-9 (2024).

Yang, L. A practical guide for structural variation detection in the human genome. CP Hum. Genet. 107, e103 (2020).

Article  CAS  Google Scholar 

Huddleston, J. & Eichler, E. E. An incomplete understanding of human genetic variation. Genetics 202, 1251–1254 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Korbel, J. O. et al. Paired-end mapping reveals extensive structural variation in the human genome. Science 318, 420–426 (2007).

Article  CAS  PubMed  PubMed Central  Google Scholar 

De Coster, W. & Van Broeckhoven, C. Newest methods for detecting structural variations. Trends Biotechnol. 37, 973–982 (2019).

Article  PubMed  Google Scholar 

Mitsuhashi, S. & Matsumoto, N. Long-read sequencing for rare human genetic diseases. J. Hum. Genet. 65, 11–19 (2020).

Article  PubMed  Google Scholar 

Nurk, S. et al. The complete sequence of a human genome. Science 376, 44–53 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aretz, S. et al. Familial adenomatous polyposis: aberrant splicing due to missense or silent mutations in the APC gene. Hum. Mutat. 24, 370–380 (2004).

Article  CAS  PubMed  Google Scholar 

Grandval, P. et al. The UMD-APC Database, a model of nation-wide knowledge base: update with data from 3,581 variations. Hum. Mutat. 35, 532–536 (2014).

Article  CAS  PubMed  Google Scholar 

Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).

Article 

Comments (0)

No login
gif