A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer.
Anticipation
Deletion
Founder mutation
Lynch syndrome
MSH2
Journal
Familial cancer
ISSN: 1573-7292
Titre abrégé: Fam Cancer
Pays: Netherlands
ID NLM: 100898211
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
04
12
2020
accepted:
29
03
2021
pubmed:
11
4
2021
medline:
6
5
2022
entrez:
10
4
2021
Statut:
ppublish
Résumé
Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.
Identifiants
pubmed: 33837488
doi: 10.1007/s10689-021-00249-x
pii: 10.1007/s10689-021-00249-x
doi:
Substances chimiques
MSH2 protein, human
EC 3.6.1.3
MutS Homolog 2 Protein
EC 3.6.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
181-188Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Chen S, Wang W, Lee S, Nafa K, Lee J, Romans K, Watson P, Gruber SB, Euhus D, Kinzler KW, Jass J, Gallinger S, Lindor NM, Casey G, Ellis N, Giardiello FM, Offit K, Parmigiani G, Registry CCF (2006) Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA 296(12):1479–1487. https://doi.org/10.1001/jama.296.12.1479
doi: 10.1001/jama.296.12.1479
pubmed: 17003396
pmcid: 2538673
Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, Haile R, Thibodeau SN, Gunawardena S, Jenkins MA, Buchanan DD, Potter JD, Baron JA, Ahnen DJ, Moreno V, Andreu M, Ponz de Leon M, Rustgi AK, Castells A, EPICOLON Consortium (2012) Identification of Lynch syndrome among patients with colorectal cancer. JAMA 308(15):1555–1565. https://doi.org/10.1001/jama.2012.13088
doi: 10.1001/jama.2012.13088
pubmed: 23073952
Møller P, Seppälä TT, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons RH, Jeffries J, Vasen HFA, Burn J, Nakken S, Hovig E, Rødland EA, Tharmaratnam K, de Vos Tot Nederveen Cappel WH, Hill J, Wijnen JT, Jenkins MA, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Valentin MD, Frayling IM, Plazzer JP, Pylvanainen K, Genuardi M, Mecklin JP, Moeslein G, Sampson JR, Capella G (2018) Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut 67(7):1306–1316. https://doi.org/10.1136/gutjnl-2017-314057 (Erratum in: Gut 2020;69(6):e4)
doi: 10.1136/gutjnl-2017-314057
pubmed: 28754778
Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM, Cavalieri RJ, Boland CR (1993) Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104(5):1535–1549. https://doi.org/10.1016/0016-5085(93)90368-m
doi: 10.1016/0016-5085(93)90368-m
pubmed: 8482467
Ponti G, Castellsagué E, Ruini C, Percesepe A, Tomasi A (2015) Mismatch repair genes founder mutations and cancer susceptibility in Lynch syndrome. Clin Genet 87(6):507–516. https://doi.org/10.1111/cge.12529
doi: 10.1111/cge.12529
pubmed: 25345868
Froggatt NJ, Joyce JA, Davies R, Gareth D, Evans R, Ponder BA, Barton DE, Maher ER (1995) A frequent hMSH2 mutation in hereditary non-polyposis colon cancer syndrome. Lancet 345(8951):727. https://doi.org/10.1016/s0140-6736(95)90900-1
doi: 10.1016/s0140-6736(95)90900-1
pubmed: 7885145
Lynch HT, de la Chapelle A, Hampel H, Wagner A, Fodde R, Lynch JF, Okimoto R, Clark MB, Coronel S, Trowonou A, Fu YX, Haynatzki GR, Gong G (2006) American founder mutation for Lynch syndrome. Prevalence estimates and implications. Cancer 106(2):448–452. https://doi.org/10.1002/cncr.21624
doi: 10.1002/cncr.21624
pubmed: 16353207
Pérez-Cabornero L, Flores EB, Sanz MI, Sampedro EV, Becares AA, Aras EL, González JC, Riu MP, Munar CG, Pino CM, Domínguez DM (2011) Characterization of new founder Alu-mediated rearrangements in MSH2 gene associated with a Lynch syndrome phenotype. Cancer Prev Res 4(10):1546–1555
doi: 10.1158/1940-6207.CAPR-11-0227
Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC (2016) Improving performance of multigene panels for genomic analysis of cancer predisposition. Genet Med 18(10):974–981. https://doi.org/10.1038/gim.2015.212
doi: 10.1038/gim.2015.212
pubmed: 26845104
Nord AS, Lee M, King MC, Walsh T (2011) Accurate and exact CNV identification from targeted high-throughput sequence data. BMC Genomics 12:184. https://doi.org/10.1186/1471-2164-12-184
doi: 10.1186/1471-2164-12-184
pubmed: 21486468
pmcid: 3088570
Tomashov-Matar R, Biran G, Lagovsky I, Kotler N, Stein A, Fisch B, Sapir O, Shohat M (2012) Severe combined immunodeficiency (SCID): from the detection of a new mutation to preimplantation genetic diagnosis. J Assist Reprod Genet 29(7):687–692. https://doi.org/10.1007/s10815-012-9765-3
doi: 10.1007/s10815-012-9765-3
pubmed: 22527898
pmcid: 3401258
Dominguez-Valentin M, Sampson JR, Møller P, Seppälä TT, Collaborators PLSD (2021) Analysis in the Prospective Lynch Syndrome Database identifies sarcoma as part of the Lynch syndrome tumor spectrum. Int J Cancer 148(2):512–513. https://doi.org/10.1002/ijc.33214
doi: 10.1002/ijc.33214
pubmed: 32783184
Warthin AS (1925) The further study of a cancer family. J Cancer Res 9:279–286
Westphalen AA, Russell AM, Buser M, Berthod CR, Hutter P, Plasilova M, Mueller H, Heinimann K (2005) Evidence for genetic anticipation in hereditary non-polyposis colorectal cancer. Hum Genet 116(6):461–465. https://doi.org/10.1007/s00439-005-1272-5
doi: 10.1007/s00439-005-1272-5
pubmed: 15772852
von Salomé J, Boonstra PS, Karimi M, Silander G, Stenmark-Askmalm M, Gebre-Medhin S, Aravidis C, Nilbert M, Lindblom A, Lagerstedt-Robinson K (2017) Genetic anticipation in Swedish Lynch syndrome families. PLoS Genet 13(10):e1007012. https://doi.org/10.1371/journal.pgen.1007012
doi: 10.1371/journal.pgen.1007012
Stella A, Surdo NC, Lastella P, Barana D, Oliani C, Tibiletti MG, Viel A, Natale C, Piepoli A, Marra G, Guanti G (2007) Germline novel MSH2 deletions and a founder MSH2 deletion associated with anticipation effects in HNPCC. Clin Genet 71(2):130–139. https://doi.org/10.1111/j.1399-0004.2007.00745.x
doi: 10.1111/j.1399-0004.2007.00745.x
pubmed: 17250661
Ten Broeke SW, Rodríguez-Girondo M, Suerink M, Aretz S, Bernstein I, Capellá G, Engel C, Gomez-Garcia EB, van Hest LP, von Knebel DM, Lagerstedt-Robinson K, Letteboer TGW, Moller P, van Os TA, Pineda M, Rahner N, Olderode-Berends MJW, von Salomé J, Schackert HK, Spruijt L, Steinke-Lange V, Wagner A, Tops CMJ, Nielsen M (2019) The apparent genetic anticipation in PMS2-associated Lynch syndrome families is explained by birth-cohort effect. Cancer Epidemiol Biomark Prev 28(6):1010–1014. https://doi.org/10.1158/1055-9965.EPI-18-0576
doi: 10.1158/1055-9965.EPI-18-0576
Talseth-Palmer BA, Wijnen JT, Grice DM, Scott RJ (2013) Genetic modifiers of cancer risk in Lynch syndrome: a review. Fam Cancer 12(2):207–216. https://doi.org/10.1007/s10689-013-9614-2
doi: 10.1007/s10689-013-9614-2
pubmed: 23471748
pmcid: 3717148
Bozzao C, Lastella P, Stella A (2011) Anticipation in Lynch syndrome: where we are where we go. Curr Genomics 12(7):451–465. https://doi.org/10.2174/138920211797904070
doi: 10.2174/138920211797904070
pubmed: 22547953
pmcid: 3219841
Ansari R, Mahdavinia M, Sadjadi A, Nouraie M, Kamangar F, Bishehsari F, Fakheri H, Semnani S, Arshi S, Zahedi MJ, Darvish-Moghadam S, Mansour-Ghanaei F, Mosavi A, Malekzadeh R (2006) Incidence and age distribution of colorectal cancer in Iran: results of a population-based cancer registry. Cancer Lett 240(1):143–147. https://doi.org/10.1016/j.canlet.2005.09.004
doi: 10.1016/j.canlet.2005.09.004
pubmed: 16288832
Bishehsari F, Mahdavinia M, Vacca M, Malekzadeh R, Mariani-Costantini R (2014) Epidemiological transition of colorectal cancer in developing countries: environmental factors, molecular pathways, and opportunities for prevention. World J Gastroenterol 20(20):6055–6072. https://doi.org/10.3748/wjg.v20.i20.6055
doi: 10.3748/wjg.v20.i20.6055
pubmed: 24876728
pmcid: 4033445
Timotewos G, Solomon A, Mathewos A, Addissie A, Bogale S, Wondemagegnehu T, Aynalem A, Ayalnesh B, Dagnechew H, Bireda W, Kroeber ES, Mikolajczyk R, Bray F, Jemal A, Kantelhardt EJ (2018) First data from a population based cancer registry in Ethiopia. Cancer Epidemiol 53:93–98. https://doi.org/10.1016/j.canep.2018.01.008
doi: 10.1016/j.canep.2018.01.008
pubmed: 29414637
The Israeli National Cancer Registry (2017) Colorectal cancer in Israel. Update incidence and mortality data, 2017. Ministry of Health, Israel. https://www.health.gov.il/English/MinistryUnits/ICDC/Chronic_Diseases/Cancer/Pages/default.aspx