RPS6KA2

Overview

RPS6KA2 (Ribosomal Protein S6 Kinase A2; also known as RSK3) encodes a serine/threonine kinase in the MAPK signaling cascade that phosphorylates downstream targets involved in cell survival, proliferation, and motility. It is located on chromosome 6q27. In adenoid cystic carcinoma (ACC), RPS6KA2 was identified as a single-tumor translocation partner of NFIB, producing an NFIB–RPS6KA2 fusion as part of the recurrent NFIB translocation landscape.

Alterations observed in the corpus

  • Single-tumor NFIB–RPS6KA2 fusion (chromosome 6q partner) identified by WGS in a 25-sample ACC cohort; one of five distinct NFIB translocation partners (MYB, MAP3K5, MYBL1, RIMS1, MYO6 also observed) PMID:26862087

Cancer types (linked)

  • ACYC (adenoid cystic carcinoma): RPS6KA2 identified as a non-recurrent fusion partner of NFIB (1/25 tumors); all NFIB fusions result in NFIB overexpression driving an oncogenic transcriptional program independent of fusion status PMID:26862087

Co-occurrence and mutual exclusivity

  • All NFIB translocation partners (including RPS6KA2) are mutually exclusive with each other within individual tumors; MYB–NFIB remains the most frequent rearrangement (11/25) PMID:26862087

Therapeutic relevance

  • No direct therapeutic data in this corpus for RPS6KA2-specific fusions; RSK family kinases are of general interest as MAPK pathway effectors but no targeted therapy is reported here.

Open questions

  • Whether the RPS6KA2 kinase domain contributes oncogenic activity in the context of the NFIB fusion protein is unknown.

Sources

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