title: Colorectal cancer DNA methylation marker panel validated with high performance in Non-Hodgkin lymphoma.
abstract: Genes with altered DNA methylation can be used as biomarkers for cancer detection and assessment of prognosis. Here we analyzed the methylation status of a colorectal cancer biomarker panel (CNRIP1, FBN1, INA, MAL, SNCA, and SPG20) in 97 cancer cell lines, derived from 17 different cancer types. Interestingly, the genes were frequently methylated also in hematological cancer types and were therefore subjected to analyses in primary tumor samples from the major types of non-Hodgkin lymphomas (NHL) and in healthy controls. In total, the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 were methylated in 53%, 23%, 52%, 69%, 97%, and 92% of the tumor samples, respectively, and were unmethylated in all healthy controls. With the exception of a single tumor sample, a correct prediction of lymphoma or normal sample was made in a blinded analysis of the validation series using a combination of SNCA and SPG20. The combined ROC-curve analysis of these genes resulted in an area under the curve of 0.999 (P = 4.2 × 10(-18)), and a sensitivity and specificity of 98% and 100%, respectively, across the test and validation series. Interestingly, the promoter methylation of CNRIP1 was associated with decreased overall survival in diffuse large B-cell lymphoma (DLBCL) (P = 0.03).   In conclusion, our results demonstrate that SNCA and SPG20 methylation might be suitable for early detection and monitoring of NHL. Furthermore, CNRIP1 could potentially be used as a prognostic factor in DLBCL.
authors.affiliation: Department of Immunology; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway; Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bethge
authors.affiliation: Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway; Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway.
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
authors.affiliation: Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway; Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway.
authors.forename: Hilde
authors.initials: H
authors.lastname: Honne
authors.affiliation: Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway; Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway.
authors.forename: Kim
authors.initials: K
authors.lastname: Andresen
authors.affiliation: Department of Pathology; Oslo University Hospital; Oslo, Norway.
authors.forename: Gunhild
authors.initials: G
authors.lastname: Trøen
authors.affiliation: Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway; Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway.
authors.forename: Mette
authors.initials: M
authors.lastname: Eknæs
authors.affiliation: Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway; Department of Informatics; University of Oslo; Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.affiliation: Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway; Department of Oncology; The Norwegian Radium Hospital; Oslo University Hospital; Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.affiliation: Department of Pathology; Oslo University Hospital; Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.affiliation: Department of Immunology; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway; Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway.
authors.forename: Erlend B
authors.initials: EB
authors.lastname: Smeland
authors.affiliation: Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway; Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital; Oslo, Norway.
authors.forename: Guro E
authors.initials: GE
authors.lastname: Lind
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D011506:Proteins; C497604:SNCA protein, human; C464787:SPART protein, human; D051844:alpha-Synuclein
keywords: CNRIP1; MAL; SNCA; SPG20; biomarker; diagnosis; epigenetic; lymphoma; methylation; prognosis