Table 2

Functional characterization of selected differentially methylated genes

Functionality of genes/gene namesIGHV mutatedIGHV unmutatedIGHV3-21Implicated role in cancerAccession numberReference
IGHV mutated and IGHV unmutated CLL       
    Tumor-suppressor genes       
        ABI3* Unmethylated Methylated  Lost in cancer cell lines, implicated in lung metastasis NM_016428.3 17  
        SCGB2A1* Unmethylated Methylated  Methylated in lung cancer NM_002407.1 18  
        VHL Unmethylated Methylated  Mutated in sporadic cell renal carcinoma and von Hippel-Lindau syndrome NT_022517.17 19  
        PPP1R3A* Methylated Unmethylated  Deregulated in colorectal cancer NM_002711.2 20  
        WISP3 Methylated Unmethylated  Loss of expression in inflammatory breast cancer NM_003880.2 21  
    Genes enhancing proliferation       
        ADORA3 Methylated Unmethylated  Activation of the NFκB pathway NM_020683.5 22  
        AIRE Methylated Unmethylated  Regulated by the PKC pathway NM_000383.1 23  
        CARD15 Methylated Unmethylated  Activation of the NFκB pathway NM_022162.1 24  
        FABP7 Methylated Unmethylated  Regulated by the MAPK/ERK pathway NM_001446.3 25  
        LOC340061 Methylated Unmethylated  Activation of the NFκB pathway NM_198282.1 26  
        PRF1 Methylated Unmethylated  Enhancing the MAPK pathway NM_005041.3 27  
        UNC5CL Methylated Unmethylated  Activation of the NFκB pathway NM_173561.1 28  
    Genes facilitating tumorigenesis       
        ANGPT2 Methylated Unmethylated  Preferentially expressed in unmutated CLL NM_001147.1 29  
        IFNB1 Methylated Unmethylated  Shown to enhance B-cell proliferation NM_002176.2 30  
        URP2 Methylated Unmethylated  Implicated in facilitating CLL tumorigenesis NM_031471.4 31  
    Antiapoptotic genes       
        BCL2 Methylated Unmethylated  Known antiapoptotic gene, up-regulated in many cancers NT_025028.13 32  
        PLD1 Unmethylated Methylated  Stimulates cell-cycle progression by repressing p53 regulation of p21 NM_002662.2 33  
    Proapoptotic genes       
        BCL10 Unmethylated Methylated  Proapoptotic genes, involved in p53 mediated cell death NM_003921.2 34  
        IL19 Methylated Unmethylated  Regulating apoptosis by activation of the STAT3 pathway NM_013371.2 35  
    Genes involved in prognosis       
        NGFR Unmethylated Methylated  Highly expressed in favorable prognostic ALL patients NM_002507.1 36  
IGHV unmutated and IGHV3-21 CLL       
    Tumor-suppressor genes       
        ABI3*  Methylated Unmethylated Lost in cancer cell lines, implicated in lung metastasis NM_016428.3 17  
        GPX3  Methylated Unmethylated Deleted or methylated in prostate cancer NM_002084.2 37  
        IGSF4*  Methylated Unmethylated Down-regulated by methylation in neuroblastoma NM_014333.2 38  
        SERPIND5*  Methylated Unmethylated Tumor-suppressive properties in breast cancer NM_002639.2 39  
        SLC22A18  Unmethylated Methylated Deregulated in several cancer forms NM_183233.1 40  
    Genes repressing proliferation       
        LDOC1  Unmethylated Methylated Implicated in repressing the NFκB pathway NM_012317.2 41  
        ZNF540  Methylated Unmethylated Involved in down-regulating the MAPK pathway NM_152606.2 42  
    Genes facilitating tumorigenesis       
        IL17RC  Unmethylated Methylated Shown to facilitate tumorigenesis in prostate cancer NM_032732.2 43  
        ANGPT2  Unmethylated Methylated Expressed in IGHV unmutated CLL NM_001147.1 29  
        FHL2  Methylated Unmethylated  NM_201556.1  
        S100A14  Unmethylated Methylated  NM_020672.1  
    Antiapoptotic genes       
        BCL2  Unmethylated Methylated Known antiapoptotic gene, up-regulated in many cancers NT_025028.13 32  
        PLD1  Methylated Unmethylated Stimulates cell-cycle progression by repressing p53 regulation of p21 NM_002662.2 33  
IGHV mutated and IGHV3-21 CLL       
    Genes enhancing proliferation       
        LOC340061 Methylated  Unmethylated Activation of the NFκB pathway NM_198282.1 26  
        PRF1 Methylated  Unmethylated Enhancing the MAPK pathway NM_005041.3 27  
        RASGRP3 Methylated  Unmethylated Regulated B-cell proliferation by facilitating B-cell receptor–RAS signaling NM_170672.1 44  
    Genes facilitating tumorigenesis       
        LMO2 Methylated  Unmethylated Known proto-oncogene, expressed in human B-cell lymphomas NM_005574.2 45  
        URP2 Methylated  Unmethylated Implicated in facilitating CLL tumorgenesis NM_031471.4 31  
        NCRMS Methylated  Unmethylated  XR_000219.2  
    Proapoptotic genes       
        TP53I3 Methylated  Unmethylated Shown to induce p53-mediated cell death NM_004881.2 46  
        BCL10 Unmethylated  Methylated Proapoptotic genes, involved in p53-mediated cell death NM_003921.2 34  
    Genes involved in prognosis       
        DNTT Methylated  Unmethylated Associated with poor prognosis in acute myeloid leukemia NM_004088.3 47  
Functionality of genes/gene namesIGHV mutatedIGHV unmutatedIGHV3-21Implicated role in cancerAccession numberReference
IGHV mutated and IGHV unmutated CLL       
    Tumor-suppressor genes       
        ABI3* Unmethylated Methylated  Lost in cancer cell lines, implicated in lung metastasis NM_016428.3 17  
        SCGB2A1* Unmethylated Methylated  Methylated in lung cancer NM_002407.1 18  
        VHL Unmethylated Methylated  Mutated in sporadic cell renal carcinoma and von Hippel-Lindau syndrome NT_022517.17 19  
        PPP1R3A* Methylated Unmethylated  Deregulated in colorectal cancer NM_002711.2 20  
        WISP3 Methylated Unmethylated  Loss of expression in inflammatory breast cancer NM_003880.2 21  
    Genes enhancing proliferation       
        ADORA3 Methylated Unmethylated  Activation of the NFκB pathway NM_020683.5 22  
        AIRE Methylated Unmethylated  Regulated by the PKC pathway NM_000383.1 23  
        CARD15 Methylated Unmethylated  Activation of the NFκB pathway NM_022162.1 24  
        FABP7 Methylated Unmethylated  Regulated by the MAPK/ERK pathway NM_001446.3 25  
        LOC340061 Methylated Unmethylated  Activation of the NFκB pathway NM_198282.1 26  
        PRF1 Methylated Unmethylated  Enhancing the MAPK pathway NM_005041.3 27  
        UNC5CL Methylated Unmethylated  Activation of the NFκB pathway NM_173561.1 28  
    Genes facilitating tumorigenesis       
        ANGPT2 Methylated Unmethylated  Preferentially expressed in unmutated CLL NM_001147.1 29  
        IFNB1 Methylated Unmethylated  Shown to enhance B-cell proliferation NM_002176.2 30  
        URP2 Methylated Unmethylated  Implicated in facilitating CLL tumorigenesis NM_031471.4 31  
    Antiapoptotic genes       
        BCL2 Methylated Unmethylated  Known antiapoptotic gene, up-regulated in many cancers NT_025028.13 32  
        PLD1 Unmethylated Methylated  Stimulates cell-cycle progression by repressing p53 regulation of p21 NM_002662.2 33  
    Proapoptotic genes       
        BCL10 Unmethylated Methylated  Proapoptotic genes, involved in p53 mediated cell death NM_003921.2 34  
        IL19 Methylated Unmethylated  Regulating apoptosis by activation of the STAT3 pathway NM_013371.2 35  
    Genes involved in prognosis       
        NGFR Unmethylated Methylated  Highly expressed in favorable prognostic ALL patients NM_002507.1 36  
IGHV unmutated and IGHV3-21 CLL       
    Tumor-suppressor genes       
        ABI3*  Methylated Unmethylated Lost in cancer cell lines, implicated in lung metastasis NM_016428.3 17  
        GPX3  Methylated Unmethylated Deleted or methylated in prostate cancer NM_002084.2 37  
        IGSF4*  Methylated Unmethylated Down-regulated by methylation in neuroblastoma NM_014333.2 38  
        SERPIND5*  Methylated Unmethylated Tumor-suppressive properties in breast cancer NM_002639.2 39  
        SLC22A18  Unmethylated Methylated Deregulated in several cancer forms NM_183233.1 40  
    Genes repressing proliferation       
        LDOC1  Unmethylated Methylated Implicated in repressing the NFκB pathway NM_012317.2 41  
        ZNF540  Methylated Unmethylated Involved in down-regulating the MAPK pathway NM_152606.2 42  
    Genes facilitating tumorigenesis       
        IL17RC  Unmethylated Methylated Shown to facilitate tumorigenesis in prostate cancer NM_032732.2 43  
        ANGPT2  Unmethylated Methylated Expressed in IGHV unmutated CLL NM_001147.1 29  
        FHL2  Methylated Unmethylated  NM_201556.1  
        S100A14  Unmethylated Methylated  NM_020672.1  
    Antiapoptotic genes       
        BCL2  Unmethylated Methylated Known antiapoptotic gene, up-regulated in many cancers NT_025028.13 32  
        PLD1  Methylated Unmethylated Stimulates cell-cycle progression by repressing p53 regulation of p21 NM_002662.2 33  
IGHV mutated and IGHV3-21 CLL       
    Genes enhancing proliferation       
        LOC340061 Methylated  Unmethylated Activation of the NFκB pathway NM_198282.1 26  
        PRF1 Methylated  Unmethylated Enhancing the MAPK pathway NM_005041.3 27  
        RASGRP3 Methylated  Unmethylated Regulated B-cell proliferation by facilitating B-cell receptor–RAS signaling NM_170672.1 44  
    Genes facilitating tumorigenesis       
        LMO2 Methylated  Unmethylated Known proto-oncogene, expressed in human B-cell lymphomas NM_005574.2 45  
        URP2 Methylated  Unmethylated Implicated in facilitating CLL tumorgenesis NM_031471.4 31  
        NCRMS Methylated  Unmethylated  XR_000219.2  
    Proapoptotic genes       
        TP53I3 Methylated  Unmethylated Shown to induce p53-mediated cell death NM_004881.2 46  
        BCL10 Unmethylated  Methylated Proapoptotic genes, involved in p53-mediated cell death NM_003921.2 34  
    Genes involved in prognosis       
        DNTT Methylated  Unmethylated Associated with poor prognosis in acute myeloid leukemia NM_004088.3 47  
*

These genes represent candidate tumor-suppressor genes.

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