Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Gene RB1
Variant loss
Impact List unknown
Protein Effect loss of function
Gene Variant Descriptions RB1 loss indicates loss of the RB1 gene, mRNA, and protein.
Associated Drug Resistance

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

No Variant Reference Transcript is Available.
No transcript is Available.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RB1 loss neuroendocrine tumor sensitive Sirolimus Preclinical Actionable In a preclinical study, Sirolimus (rapamycin) slowed pituitary tumors and decreased the occurrence of thyroid tumors in Rb1+/- mice (PMID: 23454836). 23454836
RB1 loss retinoblastoma sensitive Vorinostat Preclinical - Cell culture Actionable In a preclinical study, Zolinza (vorinostat) inhibited growth of retinoblastoma cell lines in culture (PMID: 18483379), which have been demonstrated to be deficient in RB1 (PMID: 23498719). 23498719 18483379
RB1 loss retinoblastoma sensitive Sirolimus Preclinical Actionable In a preclinical study, Sirolimus (rapamycin) decreased tumor occurrence, tumor hypoxia and tumor vascularization in a retinoblastoma mouse model with functionally inactivated Rb protein (PMID: 21468343, PMID: 1689463). 21468343 1689463
RB1 loss retinoblastoma sensitive Entinostat Preclinical - Cell line xenograft Actionable In a preclinical study, Entinostat (MS-275) inhibited growth of retinoblastoma cell lines in culture and inhibited tumor growth in a retinoblastoma cell line xenograft model (PMID: 18483379), which have been demonstrated to be deficient in RB1 (PMID: 23498719). 23498719 18483379
RB1 loss lung small cell carcinoma resistant Trilaciclib Preclinical - Cell line xenograft Actionable In a preclinical study, RB1-deficient small cell lung cancer cell lines were resistant to Trilaciclib (G1T28) in culture and in xenograft models (PMID: 26826116). 26826116
RB1 loss Advanced Solid Tumor no benefit Palbociclib Preclinical Actionable In preclinical studies, the CDK4/6 inhibitor, Ibrance (palbociclib), was not effective in a variety of solid tumors with Rb1-deficiency (PMID: 26649278). 26649278
RB1 loss estrogen-receptor positive breast cancer resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, RB1 loss was associated with acquired resistance to Ibrance (palbociclib) in an estrogen-receptor positive breast cancer cell line in culture (PMID: 27020857). 27020857
RB1 loss lung small cell carcinoma sensitive Topotecan + Trilaciclib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Trilaciclib (G1T28) and Hycamtin (topotecan) inhibited tumor growth in RB1-deficient small cell lung cancer cell line xenograft models, with greater efficacy than Hycamtin (topotecan) alone (PMID: 26826116). 26826116
RB1 loss retinoblastoma sensitive Trichostatin A Preclinical - Cell culture Actionable In a preclinical study, Trichostatin A (TSA) inhibited growth of retinoblastoma cell lines in culture (PMID: 18483379), which have been demonstrated to be deficient in RB1 (PMID: 23498719). 23498719 18483379
BRAF mut RB1 loss melanoma decreased response Palbociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and loss of RB1 demonstrated a decreased response to Ibrance (palbociclib) treatment in culture when compared to treatment of melanoma cell lines wild-type for BRAF (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and RB1 loss demonstrated reduced sensitivity when treated with Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
NOTCH1 wild-type RB1 loss T-cell adult acute lymphocytic leukemia resistant Ribociclib Preclinical - Cell culture Actionable In a preclinical study, a T-cell acute lymphoblastic leukemia cell line harboring wild-type NOTCH1 and loss of RB1 demonstrated resistance to Kisqali (ribociclib) in culture, resulting in limited inhibition of cell growth (PMID: 28151717). 28151717
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RB1 inact mut retinoblastoma sensitive Nutlin-3a Preclinical Actionable In a preclinical study, Nutlin-3a induced p53 pathway signaling in MDMX mouse models with retinoblastoma and 69% (70/102) of the eyes harvested from the mouse models demonstrated complete response or stable disease after 18 weeks of therapy (PMID: 21515735). 21515735
RB1 inact mut glioblastoma multiforme resistant Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, Ibrance (palbociclib) failed to inhibit growth of RB1-deficient glioblastoma cell lines in culture and in intracranial cell line xenograft models (PMID: 20354191). 20354191
RB1 inact mut retinoblastoma sensitive Fostamatinib Preclinical Actionable In a preclinical study, retinoblastoma cell lines demonstrated sensitivity to Fostamatinib resulting in cell death (PMID: 22237022). 22237022
RB1 inact mut retinoblastoma sensitive BAY 61-3606 Preclinical Actionable In a preclinical study, a retinoblastoma cell line was sensitive to BAY 61-3606 in cell culture and in xenograft models, demonstrating increased apoptosis (PMID: 22237022). 22237022
RB1 mutant osteosarcoma sensitive VCN-01 Preclinical - Cell line xenograft Actionable In a preclinical study, VCN-01 decreased viability of a human RB1-mutant primary osteosarcoma cell line in culture, and inhibited tumor growth and decreased lung metastases in xenograft models (PMID: 26603261). 26603261
RB1 mutant estrogen-receptor positive breast cancer predicted - resistant Palbociclib Phase III Actionable In a Phase III trial (PALOMA-3), acquired RB1 mutations were identified in patents with ER-positive, ERBB2 (HER2)-negative breast cancer at the end of treatment in the Faslodex (fulvestrant) plus Ibrance (palbociclib) but not the Faslodex (fulvestrant) plus placebo arm, suggesting a role in conferring resistance to Ibrance (palbociclib) (PMID: 30206110; NCT01942135). 30206110
Molecular Profile Protein Effect Treatment Approaches
RB1 loss loss of function HDAC Inhibitor
BRAF mut RB1 loss
NOTCH1 wild-type RB1 loss