• What is ZRSR2?
  • ZRSR2 in Myelodysplastic Syndromes
  • ZRSR2 Mutations
  • Clinical Trials

ZRSR2

Zinc finger (CCCH type), RNA-binding motif and serine/arginine rich 2 (ZRSR2) is a gene that encodes for a member of the spliceosome. The protein coded by this gene associates with the U2 auxiliary factor, which plays an important role in RNA splicing (Gene 2014). Spliceosome mutations are observed in MDS, chronic lymphocytic leukemia (CLL), AML, and chronic myelomonocytic leukemia (CMML), and these mutations can cause abnormal expression patterns of some genes involved in cancer pathogenesis (Chesnais et al. 2012).​

Related Pathways

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. ZRSR2. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/zrsr2/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

ZRSR2 in Myelodysplastic Syndromes

ZRSR2 mutations occur in 6.8% of MDS (COSMIC). The role of ZRSR2 mutations in MDS is not yet well understood (Cazzola, Della Porta, and Malcovati 2013). Unlike many of the other spliceosome genes, mutations in ZRSR2 are found throughout the gene without recurrent sites of mutations.

ZRSR2 mutations have been associated with neutral or unfavorable outcomes. Thol et al. (2012) observed no impact of ZRSR2 mutations on outcomes of 193 MDS patients, while Damm et al. (2012) observed shorter overall survival and higher likelihood of transformation to AML for patients with ZRSR2 mutations and no mutation in TET2 in a study of 221 MDS patients.​

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. ZRSR2 in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/zrsr2/ (Updated October 16).

Last Updated: October 16, 2015

ZRSR2 Mutations in Myelodysplastic Syndromes

Properties
Location of mutations ZRSR2 gene on Xp22.1
Frequency of ZRSR2 mutations in MDS 6.8% (COSMIC)
Implications for Targeted Therapeutics
Response to bromodomain inhibitors, DOT1L inhibitors, or other targeted epigenetic therapies Unknown at this timea
Response to spliceosome-targeting therapies Unknown at this timeb
Response to Ras-targeting therapies Unknown at this timec

ZRSR2 mutations have been associated with neutral or unfavorable outcomes. Thol et al. (2012) observed no impact of ZRSR2 mutations on outcomes of 193 MDS patients, while Damm et al. (2012) observed shorter overall survival and higher likelihood of transformation to AML for patients with ZRSR2 mutations and no mutation in TET2 in a study of 221 MDS patients.

a Bromodomain (BRD2, BRD3, BRD4, and BRDt) inhibitors and DOT1L inhibitors are in phase I studies in hematologic malignancies (Abdel-Wahab and Levine 2013). In addition, several other epigenetic targeted therapies, targeting IDH1/IDH2, EZH2, LSD1, or UTX/JMJD3, are in development (Abdel-Wahab and Levine 2013).

b Drugs targeting the spliceosome are in development; these drugs alter gene expression or affect alternative splicing in ways that inhibit cancer progression (Bonnal, Vigevani, and Valcarcel 2012).

c Efforts to develop Ras-targeting therapies are in progress and are hoped to be useful in hematologic malignancies (Ward, Braun, and Shannon 2012).

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. ZRSR2 Mutations in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/zrsr2/333/ (Updated October 16).

Last Updated: October 16, 2015

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