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    BIOMARKER:

    CDKN2B deletion

    i
    Other names: CDKN2B, Cyclin Dependent Kinase Inhibitor 2B, Cyclin-Dependent Kinase Inhibitor 2B (P15, Inhibits CDK4), Cyclin-Dependent Kinase 4 Inhibitor B, Multiple Tumor Suppressor, P14-INK4b, P15-INK4b, MTS-2, MTS2, Cyclin-Dependent Kinases 4 And 6 Binding Protein, CDK Inhibitory Protein, P14_CDK Inhibitor, P15 CDK Inhibitor, CDK4B Inhibitor, P14_INK4B, P15_INK4B, P15INK4b, P15INK4B, CDK4I, INK4B, TP15, P15
    Entrez ID:
    1030
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    4ms
    Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: LACOG 2018 translational study. (PubMed, Oncologist)
    This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.
    Clinical data • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    PD-L1 expression • NOTCH1 mutation • CDKN2B deletion
    1year
    Molecular characterization of metastatic penile carcinoma (mPC) in developing countries and its association with clinical outcomes: LACOG 2018 FOUNDATION translational trial. (ASCO-GU 2024)
    This translational study demonstrated that molecular alterations in mPC in developing countries are similar to those in patients from developed countries. Predictive biomarkers for immunotherapy, such as TMB high or MSI, were not identified in this study cohort. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.
    Clinical data • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    PD-L1 expression • TMB-L • NOTCH1 mutation • CDKN2B deletion
    |
    FoundationOne® CDx
    over1year
    Genomic heterogeneity of ALK rearrangements and acquired resistance pathways in ALK+ Advanced non-small cell lung cancer (NSCLC) treated with upfront alectinib: Preliminary results of GALILEO project (ESMO 2023)
    Legal entity responsible for the study Fondazione Policlinico Universitario A Gemelli – IRCCS. In post-lorlatinib NGS-assay, 2 pts had ALK-compound mutations, while 4 pts had newly off-target alterations (CDKN2A/B CDKN2B loss, NF1 deletion, DNMT3A/ARID1A/CHECK2 M+). Conclusions Implementation of longitudinal genomic assessment is required in order to provide an extensive overview of resistance mechanisms and clinical outcomes according to current ALK-inhibitors treatment sequences.
    Preclinical • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK mutation • CDKN2A deletion • ALK G1202R • NF1 deletion • ALK I1171N • ALK I1171 • ALK E1210K • CDKN2B deletion • EML4-ALK G1202R
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Alecensa (alectinib) • Lorbrena (lorlatinib)
    over1year
    Clinical outcomes and genomic landscape of patients (pts) with EGFR-mutant lung cancer (EGFR+ LC) with central nervous system (CNS) metastases (mets). (ASCO 2023)
    All pts treated with 1L osimertinib with MSK-IMPACT available on their STS were also identified... In patients with EGFR+ LC, there were no genomic alterations that were significantly enriched in CNS mets compared to systemic disease, and no systemic genomic alterations that differentiate pts w/wo CNS mets.
    Clinical data • Clinical
    |
    EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CARD11 (Caspase Recruitment Domain Family Member 11) • RAC1 (Rac Family Small GTPase 1)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • CDKN2B deletion
    |
    MSK-IMPACT
    |
    Tagrisso (osimertinib)
    almost2years
    Clinical use of next-generation sequencing panel in pediatric oncology patients (AACR 2023)
    Fifteen patients (10.7%) were enrolled in clinical trials or compassionate use program according to molecular profiling (DAY101 [BRAF inhibitor] in 3, selpercatinib in 3, palbociclib in 2, olaparib in 2, alectinib in 1, repotrectinib in 1, larotrectinib in 1, atezolizumab in 1 and erdafitinib in 1). Two (1.4%), one (0.7%) and one (0.7%) patients received vemurafenib, larotrectinib, and pembrolizumab with non-reimbursement... Application of NGS panel in pediatric cancer aid in diagnosis, treatment decision, clinical trial enrollment and germline risk determination. Although there are not many cases linked with molecular target-based therapy, it is leading to clinical benefits in pediatric patients and more understanding genomic profiling of pediatric cancer.
    Clinical • Next-generation sequencing • Tumor mutational burden • PARP Biomarker • PD(L)-1 Biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • EWSR1 (EWS RNA Binding Protein 1) • CCND3 (Cyclin D3) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    TP53 mutation • TMB-H • BRAF mutation • MYCN amplification • CDKN2B deletion
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • Zelboraf (vemurafenib) • Vitrakvi (larotrectinib) • Alecensa (alectinib) • Balversa (erdafitinib) • Retevmo (selpercatinib) • Augtyro (repotrectinib)
    over2years
    Comprehensive Landscape of Cyclin Pathway Gene Alterations and Co-occurrence with FGF/FGFR Aberrations Across Urinary Tract Tumors. (PubMed, Oncologist)
    Cyclin pathway activating alterations are common in urinary tract tumors, but frequency varies with histology and tumors sites. Co-occurrence of cyclin and FGFR pathway alterations may inform therapeutic opportunities.
    Journal
    |
    FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • FGFR (Fibroblast Growth Factor Receptor) • CCNE1 (Cyclin E1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    CDKN2B deletion
    3years
    Genomic Classification of Clinically Advanced Prostate Cancer (CAPC) Based on Methylthioadenosine Phosphorylase (MTAP) Genomic Loss (USCAP 2022)
    A small number of cases of CAPC have MTAP loss (1.3%). MTAP loss is associated with a higher mean TMB, and has a significantly different GA profile, indicating a potential benefit for directed therapy of CAPC based on MTAP status. Of particular interest, CAPC with MTAP loss has lower frequencies of GA in AR, CDK12 and RB1, and higher frequencies of GA in CDKN2A, CDKN2B, TP53.
    Clinical • Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • MTAP (Methylthioadenosine Phosphorylase) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ERG (ETS Transcription Factor ERG) • SPOP (Speckle Type BTB/POZ Protein) • RAD21 (RAD21 Cohesin Complex Component)
    |
    PD-L1 expression • CDKN2A deletion • SPOP mutation • TMPRSS2-ERG fusion • CDKN2B deletion • PTEN overexpression
    |
    PD-L1 IHC 22C3 pharmDx
    over3years
    [VIRTUAL] Comprehensive molecular profiling of pleural mesothelioma according to histologic subtype. (ASCO 2021)
    Compared to epithelioid MPM, non-epithelioid tumors demonstrate comparable TMB, higher PD-L1 expression, and enrichment for MTAP loss . As MTAP is frequently altered in MPM, further study is indicated to explore the relationship between MTAP status and MPM biology, including sensitivity to therapeutics such as immunotherapy and synthetic lethal approaches.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1)
    |
    PD-L1 expression • CDKN2B deletion
    |
    PD-L1 IHC 22C3 pharmDx
    4years
    [VIRTUAL] In search of novel synthetic lethality anti-cancer drug targets in intrahepatic cholangiocarcinoma: MTAP genomic loss. (ASCO-GI 2021)
    Comprehensive genomic profiling elucidated that MTAP GA are frequent in IC and features relatively high GA/tumor, including 9p21 co-deletion, but relatively low TMB and PD-L1 expression. Isolated MTAP deletion without CDKN2A/B co-deletion was extremely rare. In addition to the potential targeting of PRMT5 in MTAP-IC tumors, co-altered genes known to be targets in IC such as FGFR2, IDH1 and BRAF are still prevalent in MTAP-IC, indicating potential for combining targeted therapies in some MTAP-IC patients.
    Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • SMAD4 (SMAD family member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • BRCA (Breast cancer early onset) • PRMT5 (Protein Arginine Methyltransferase 5)
    |
    PD-L1 expression • TP53 mutation • BRAF V600E • KRAS mutation • MSI-H/dMMR • KRAS G12C • HER-2 amplification • BRAF V600 • MET amplification • PD-L1 underexpression • PD-L1 negative • TMB-L • CDKN2A deletion • MTAP deletion • KRAS G12 • CDKN2B deletion • HER-2 amplification + PD-L1 expression • KRAS deletion • miR-138 underexpression + miR-497 overexpression
    |
    FoundationOne® CDx • PD-L1 IHC 22C3 pharmDx
    4years
    [VIRTUAL] Mutational Profile May Aid in Diagnosis of Undifferentiated/Dedifferentiated Melanoma (ASDP 2020)
    Undifferentiated/dedifferentiated melanoma is a diagnostic challenge by standard immunohistochemical methods. Identification of mutations that are common in melanoma may be a useful adjunct in the diagnosis of these challenging cases.
    IO biomarker
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TSC1 (TSC complex subunit 1) • CD163 (CD163 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • VIM (Vimentin) • TP63 (Tumor protein 63)
    |
    BRAF V600E • NRAS mutation • BRAF V600 • NRAS Q61K • NRAS Q61 • CDKN2B deletion • miR-138 underexpression + miR-497 overexpression