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AT-rich interactive domain-containing protein 1B (ARID domain-containing protein 1B) (BRG1-associated factor 250b) (BAF250B) (BRG1-binding protein hELD/OSA1) (Osa homolog 2) (hOsa2) (p250R) [BAF250B] [DAN15] [KIAA1235] [OSA2]


A 69-year-old woman with Coffin-Siris syndrome.

Coffin-Siris syndrome (CSS) is a rare intellectual disability syndrome classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and other digits, distinctive facial features, hirsutism/hypertrichosis, and sparce scalp hair. It is genetically heterogeneous but most often caused by a pathogenic variant in the ARID1B gene. Previous clinical reports of CSS patients are mainly based on young or middle-aged individuals. Here, we report a 69-year-old woman with CSS phenotype and a pathogenic ARID1B loss-of-function variant c.5259_5260dup. She has severe intellectual disability but otherwise she is in relatively good health both physically and mentally. There is no evident history of chronic illness or progressive disability. CSS appears to be compatible with long survival and most likely it is underdiagnosed in geriatric patients with intellectual disability.

MeSH Terms

  • Abnormalities, Multiple
  • Aged
  • DNA-Binding Proteins
  • Face
  • Female
  • Hand Deformities, Congenital
  • Humans
  • Intellectual Disability
  • Loss of Function Mutation
  • Micrognathism
  • Neck
  • Transcription Factors


  • ARID1B
  • Coffin-Siris syndrome
  • geriatrics
  • intellectual disability

SWI/SNF regulates a transcriptional program that induces senescence to prevent liver cancer.

Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumors. ARID1B controls p16 and p21 transcription but also regulates DNA damage, oxidative stress, and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence. To systematically identify SWI/SNF targets regulating senescence, we carried out a focused shRNA screen. We discovered several new senescence regulators, including ENTPD7, an enzyme that hydrolyses nucleotides. ENTPD7 affects oxidative stress, DNA damage, and senescence. Importantly, expression of ENTPD7 or inhibition of nucleotide synthesis in ARID1B-depleted cells results in re-establishment of senescence. Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that prosenescence therapies could be employed against SWI/SNF-mutated cancers.

MeSH Terms

  • Animals
  • Apyrase
  • Carcinoma, Hepatocellular
  • Cell Line
  • Cell Line, Tumor
  • Cellular Senescence
  • DNA-Binding Proteins
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • RNA, Small Interfering
  • Transcription Factors


  • ARID1B
  • ENTPD7
  • cancer
  • dNTP metabolism
  • p53
  • senescence