Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer

被引：32

作者：

Castillejo, Adela ^{[1
]}

Hernandez-Illan, Eva ^{[2
]}

Rodriguez-Soler, Maria ^{[2
,3
]}

Perez-Carbonell, Lucia ^{[2
]}

Egoavil, Cecilia ^{[4
]}

Barbera, Victor M. ^{[1
]}

Castillejo, Maria-Isabel ^{[1
]}

Guarinos, Carla ^{[2
]}

Martinez-de-Duenas, Eduardo ^{[5
]}

Juan, Maria-Jose ^{[6
]}

Sanchez-Heras, Ana-Beatriz ^{[7
]}

Garcia-Casado, Zaida ^{[8
]}

Ruiz-Ponte, Clara ^{[9
]}

Brea-Fernandez, Alejandro ^{[9
]}

Juarez, Miriam ^{[2
]}

Bujanda, Luis ^{[10
]}

Clofent, Juan ^{[11
]}

Llor, Xavier ^{[12
,13
]}

Andreu, Montserrat ^{[14
]}

Castells, Antoni ^{[15
]}

Carracedo, Angel

Alenda, Cristina ^{[4
]}

Paya, Artemio ^{[4
]}

Jover, Rodrigo ^{[3
]}

Soto, Jose-Luis ^{[1
]}

机构：

[1] Elche Univ Hosp, Mol Genet Lab, Elche 03203, Spain

[2] Alicante Univ Hosp, Res Lab, Alicante, Spain

[3] Alicante Univ Hosp, Dept Gastroenterol, Alicante, Spain

[4] Alicante Univ Hosp, Dept Pathol, Alicante, Spain

[5] Consorcio Prov Hosp, Dept Med Oncol, Castellon de La Plana, Spain

[6] Valencian Inst Oncol, Hereditary Canc Unit, Valencia, Spain

[7] Elche Univ Hosp, Genet Counseling Canc Unit, Elche, Spain

[8] Valencian Inst Oncol, Mol Biol Lab, Valencia, Spain

[9] Univ Santiago de Compostela, Galician Publ Fdn Genom Med FPGMX, Genom Med Grp, Hosp Clin Santiago de Compostela,CIBERER, Santiago De Compostela, Spain

[10] Univ Basque Country UPV EHU, Dept Gastroenterol, Donostia Hosp, Inst Biodonostia,CIBERehd, San Sebastian, Spain

[11] Hosp Sagunto, Dept Internal Med, Sect Digest Dis, Sagunto, Spain

[12] Univ Illinois, Dept Med, Sect Digest Dis & Nutr, Chicago, IL USA

[13] Univ Illinois, Ctr Canc, Chicago, IL USA

[14] Pompeu Fabra Univ, Hosp del Mar, Dept Gastroenterol, IMIM, Barcelona, Spain

[15] Univ Barcelona, IDIBAPS, Dept Gastroenterol, CIBERehd,Hosp Clin, Barcelona, Spain

来源：

JOURNAL OF MEDICAL GENETICS | 2015年 / 52卷 / 07期

关键词：

COLON-CANCER; SUSCEPTIBILITY; IDENTIFICATION; INHERITANCE; VARIANTS; MUTATION; RISK;

D O I：

10.1136/jmedgenet-2015-103076

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background The prevalence of MLH1 constitutional epimutations in the general population is unknown. We sought to analyse the prevalence of MLH1 constitutional epimutations in unselected and selected series of patients with colorectal cancer (CRC). Methods Patients with diagnoses of CRC (n=2123) were included in the unselected group. For comparison, a group of 847 selected patients with CRC who fulfilled the revised Bethesda guidelines (rBG) were also included. Somatic and constitutional MLH1 methylation was assayed via methylation-specific multiplex ligation-dependent probe amplification of cases lacking MLH1 expression. Germline alterations in mismatch-repair (MMR) genes were assessed via Sanger sequencing and methylation-specific multiplex ligation-dependent probe amplification. Results Loss of MLH1 expression occurred in 5.5% of the unselected series and 12.5% of the selected series (p<0.0001). No constitutional epimutations in MLH1 were detected in the unselected population (0/62); five cases from the selected series were positive for MLH1 epimutations (15.6%, 5/32; p=0.004). Conclusions Our results suggest a negligible prevalence of MLH1 constitutional epimutations in unselected cases of CRC. Therefore, MLH1 constitutional epimutation analysis should be conducted only for patients who fulfil the rBG and who lack MLH1 expression with methylated MLH1.

引用

页码：498 / 502

页数：5

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