TY - JOUR
T1 - Methylation alteration of SHANK1 as a predictive, diagnostic and prognostic biomarker for chronic lymphocytic leukemia
AU - Loi, Eleonora
AU - Moi, Loredana
AU - Fadda, Antonio
AU - Satta, Giannina
AU - Zucca, Mariagrazia
AU - Sanna, Sonia
AU - Nia, Shadi Amini
AU - Cabras, Giuseppina
AU - Padoan, Marina
AU - Magnani, Corrado
AU - Miligi, Lucia
AU - Piro, Sara
AU - Gentilini, Davide
AU - Ennas, Maria Grazia
AU - Southey, Melissa C.
AU - Giles, Graham G.
AU - Doo, Nicole Wong
AU - Cocco, Pierluigi
AU - Zavattari, Patrizia
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the clonal expansion of malignant B cells. To predict the clinical course of the disease, the identification of diagnostic biomarkers is urgently needed. Aberrant methylation patterns may predict CLL development and its course, being very early changes during carcinogenesis. Our aim was to identify CLL specific methylation patterns and to evaluate whether methylation aberrations in selected genes are associated with changes in gene expression. Here, by performing a genome-wide methylation analysis, we identified several CLL-specific methylation alterations. We focused on the most altered one, at a CpG island located in the body of SHANK1 gene, in our CLL cases compared to healthy controls. This methylation alteration was successfully validated in a larger cohort including 139 CLL and 20 control in silico samples. We also found a positive correlation between SHANK1 methylation level and absolute lymphocyte count, in particular CD19+ B cells, in CLL patients. Moreover, we were able to detect gains of methylation at SHANK1 in blood samples collected years prior to diagnosis. Overall, our results suggest methylation alteration at this SHANK1 CpG island as a biomarker for risk and diagnosis of CLL, and also in the personalized quantification of tumor aggressiveness.
AB - Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the clonal expansion of malignant B cells. To predict the clinical course of the disease, the identification of diagnostic biomarkers is urgently needed. Aberrant methylation patterns may predict CLL development and its course, being very early changes during carcinogenesis. Our aim was to identify CLL specific methylation patterns and to evaluate whether methylation aberrations in selected genes are associated with changes in gene expression. Here, by performing a genome-wide methylation analysis, we identified several CLL-specific methylation alterations. We focused on the most altered one, at a CpG island located in the body of SHANK1 gene, in our CLL cases compared to healthy controls. This methylation alteration was successfully validated in a larger cohort including 139 CLL and 20 control in silico samples. We also found a positive correlation between SHANK1 methylation level and absolute lymphocyte count, in particular CD19+ B cells, in CLL patients. Moreover, we were able to detect gains of methylation at SHANK1 in blood samples collected years prior to diagnosis. Overall, our results suggest methylation alteration at this SHANK1 CpG island as a biomarker for risk and diagnosis of CLL, and also in the personalized quantification of tumor aggressiveness.
KW - Cancer methylation alteration
KW - Diagnostic biomarkers
KW - Predictive biomarkers
KW - Prognostic biomarkers
KW - SHANK1
UR - http://www.scopus.com/inward/record.url?scp=85071043800&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.27080
DO - 10.18632/oncotarget.27080
M3 - Article
AN - SCOPUS:85071043800
SN - 1949-2553
VL - 10
SP - 4987
EP - 5002
JO - Oncotarget
JF - Oncotarget
IS - 48
ER -
