Methylation alteration of SHANK1 as a predictive, diagnostic and prognostic biomarker for chronic lymphocytic leukemia

Eleonora Loi, Loredana Moi, Antonio Fadda, Giannina Satta, Mariagrazia Zucca, Sonia Sanna, Shadi Amini Nia, Giuseppina Cabras, Marina Padoan, Corrado Magnani, Lucia Miligi, Sara Piro, Davide Gentilini, Maria Grazia Ennas, Melissa C. Southey, Graham G. Giles, Nicole Wong Doo, Pierluigi Cocco, Patrizia Zavattari

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)4987-5002
Number of pages16
Issue number48
Publication statusPublished - 1 Aug 2019


  • Cancer methylation alteration
  • Diagnostic biomarkers
  • Predictive biomarkers
  • Prognostic biomarkers
  • SHANK1

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