Table 1

Selected recurrent genomic lesions in MCL

GeneClass/productFunctionLocusLesionReference
Cell-cycle control and DNA damage pathways      
    CCND1 Cyclin D1 Forms holoenzyme with CDK4/CDK6 to regulate G1/S transition through Rb phosphorylation 11q13 + 31  
    CDK4 Cyclin-dependent kinase Forms complex with D-type cyclins to regulate early G1 phase 12q13 + 25  
    BMI1 Oncogene Regulates cell cycle and senescence as a transcriptional repressor of INK4a/ARF locus 10p11 + 25, 125  
    MYC Oncogene Induces mitogen-independent cell proliferation; often overexpressed in cancer 8q21 + 25  
    MDM2 Negative regulator of p53 E3 ligase for p53 targeting it for proteasomal degradation 12q13 + 126  
    RB1 Tumor suppressor Binds to E2F1, preventing its nuclear translocation and cell-cycle progression 13q14.2 − 31, 127  
    CDKN2C CDK inhibitor p18 Inhibits the activity of CDK/cyclin D complexes at G1 1p32 − 31, 99  
    CDKN2A CDK inhibitor encodes p14 and p16 Inhibit the activity of CDK/cyclin D complexes at G1 9p21 − 128  
    P53 Tumor suppressor Induces cell-cycle arrest, apoptosis, and senescence 17p13 − 25  
    ATM Ser/Thr kinase of PI-3K family After DNA damage ATM controls G1/S and G2/M cell-cycle checkpoints by phosphorylation p53, MDM2, and CHK2 11q22 − 129  
    HIC1 Tumor suppressor cooperates with p53 Loss of HIC1 results in deacetylation and inactivation of p53 by reducing DNA binding 17p13.3 − 130  
    MOBKL2B Protein kinase Essential for spindle pole body duplication and mitotic checkpoint regulation 9p21.2 − 31  
Signaling pathways      
    SYK Tyr kinase Involved in BCR signaling, mediates activation of PKCβ, ΝF-κB, and PI3K-AKT pathways 9q22 + 37  
    PIK3CA PI3K catalytic subunit α (p110α) Sufficient to support survival of B cells with defective BCR signaling; AKT activation 3q25 + 70  
    FAF1 Inhibitor of ΝF-κB activation Suppresses IKK activity by binding to IKKβ, resulting in p65 retention in the cytoplasm 1p32.3 − 31  
    TNFAIP3 A20 tumor suppressor Inhibits ΝF-κB activation through ubiquitin editing 6p23 − 88  
Apoptosis      
    BCL2 Key antiapoptotic regulator Promotes cell survival by sequestering proapoptotic BAX and BAK 18q11-23 + 31  
    BCL2L11 BIM, BH3-only protein Binds to BCL2, BCLXL, and MCL1, acting as an apoptotic activator 2q13 − 31, 99  
Other pathways      
    PRAME Possible tumor antigen Expressed in solid tumors and some hematopoietic neoplasias 22q11.22 − 31  
    MAP2 Microtubule stabilizer Regulator of microtubule dynamics, cancer cell migration 2q34 − 31  
    SP100 Transcription factor Localizes to nuclear bodies; coactivator of HIPK2/p53-mediated transcription. 2q37 − 31  
    MTAP Enzyme Polyamine metabolism, frequently codeleted with the p16 9p21.3 − 31  
GeneClass/productFunctionLocusLesionReference
Cell-cycle control and DNA damage pathways      
    CCND1 Cyclin D1 Forms holoenzyme with CDK4/CDK6 to regulate G1/S transition through Rb phosphorylation 11q13 + 31  
    CDK4 Cyclin-dependent kinase Forms complex with D-type cyclins to regulate early G1 phase 12q13 + 25  
    BMI1 Oncogene Regulates cell cycle and senescence as a transcriptional repressor of INK4a/ARF locus 10p11 + 25, 125  
    MYC Oncogene Induces mitogen-independent cell proliferation; often overexpressed in cancer 8q21 + 25  
    MDM2 Negative regulator of p53 E3 ligase for p53 targeting it for proteasomal degradation 12q13 + 126  
    RB1 Tumor suppressor Binds to E2F1, preventing its nuclear translocation and cell-cycle progression 13q14.2 − 31, 127  
    CDKN2C CDK inhibitor p18 Inhibits the activity of CDK/cyclin D complexes at G1 1p32 − 31, 99  
    CDKN2A CDK inhibitor encodes p14 and p16 Inhibit the activity of CDK/cyclin D complexes at G1 9p21 − 128  
    P53 Tumor suppressor Induces cell-cycle arrest, apoptosis, and senescence 17p13 − 25  
    ATM Ser/Thr kinase of PI-3K family After DNA damage ATM controls G1/S and G2/M cell-cycle checkpoints by phosphorylation p53, MDM2, and CHK2 11q22 − 129  
    HIC1 Tumor suppressor cooperates with p53 Loss of HIC1 results in deacetylation and inactivation of p53 by reducing DNA binding 17p13.3 − 130  
    MOBKL2B Protein kinase Essential for spindle pole body duplication and mitotic checkpoint regulation 9p21.2 − 31  
Signaling pathways      
    SYK Tyr kinase Involved in BCR signaling, mediates activation of PKCβ, ΝF-κB, and PI3K-AKT pathways 9q22 + 37  
    PIK3CA PI3K catalytic subunit α (p110α) Sufficient to support survival of B cells with defective BCR signaling; AKT activation 3q25 + 70  
    FAF1 Inhibitor of ΝF-κB activation Suppresses IKK activity by binding to IKKβ, resulting in p65 retention in the cytoplasm 1p32.3 − 31  
    TNFAIP3 A20 tumor suppressor Inhibits ΝF-κB activation through ubiquitin editing 6p23 − 88  
Apoptosis      
    BCL2 Key antiapoptotic regulator Promotes cell survival by sequestering proapoptotic BAX and BAK 18q11-23 + 31  
    BCL2L11 BIM, BH3-only protein Binds to BCL2, BCLXL, and MCL1, acting as an apoptotic activator 2q13 − 31, 99  
Other pathways      
    PRAME Possible tumor antigen Expressed in solid tumors and some hematopoietic neoplasias 22q11.22 − 31  
    MAP2 Microtubule stabilizer Regulator of microtubule dynamics, cancer cell migration 2q34 − 31  
    SP100 Transcription factor Localizes to nuclear bodies; coactivator of HIPK2/p53-mediated transcription. 2q37 − 31  
    MTAP Enzyme Polyamine metabolism, frequently codeleted with the p16 9p21.3 − 31  

+ indicates amplification; and −, deletion/mutation.

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