Virchows Arch DOI 10.1007/s00428-014-1678-3
ORIGINAL ARTICLE
Heterogeneity of DNA methylation in multifocal prostate cancer Inga Serenaite & Kristina Daniunaite & Feliksas Jankevicius & Arvydas Laurinavicius & Donatas Petroska & Juozas R. Lazutka & Sonata Jarmalaite
Received: 3 July 2014 / Revised: 17 September 2014 / Accepted: 23 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (≥75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of Electronic supplementary material The online version of this article (doi:10.1007/s00428-014-1678-3) contains supplementary material, which is available to authorized users. I. Serenaite : K. Daniunaite : J. R. Lazutka : S. Jarmalaite Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania F. Jankevicius : A. Laurinavicius : D. Petroska Faculty of Medicine, Vilnius University, Vilnius, Lithuania F. Jankevicius Urology Centre, Vilnius University, Vilnius, Lithuania A. Laurinavicius : D. Petroska National Centre of Pathology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania S. Jarmalaite (*) Division of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Ciurlionio 21, 03101 Vilnius, Lithuania e-mail: [email protected]
DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p
ORIGINAL ARTICLE
Heterogeneity of DNA methylation in multifocal prostate cancer Inga Serenaite & Kristina Daniunaite & Feliksas Jankevicius & Arvydas Laurinavicius & Donatas Petroska & Juozas R. Lazutka & Sonata Jarmalaite
Received: 3 July 2014 / Revised: 17 September 2014 / Accepted: 23 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (≥75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of Electronic supplementary material The online version of this article (doi:10.1007/s00428-014-1678-3) contains supplementary material, which is available to authorized users. I. Serenaite : K. Daniunaite : J. R. Lazutka : S. Jarmalaite Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania F. Jankevicius : A. Laurinavicius : D. Petroska Faculty of Medicine, Vilnius University, Vilnius, Lithuania F. Jankevicius Urology Centre, Vilnius University, Vilnius, Lithuania A. Laurinavicius : D. Petroska National Centre of Pathology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania S. Jarmalaite (*) Division of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, Ciurlionio 21, 03101 Vilnius, Lithuania e-mail: [email protected]
DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p
