WHSC1L1

Overview

WHSC1L1 (Wolf-Hirschhorn Syndrome Candidate 1-Like 1), now designated NSD3 (Nuclear Receptor Binding SET Domain Protein 3) by HUGO, is a histone H3K36 methyltransferase located at 8p11.23. In prostate cancer, WHSC1L1 is recurrently co-amplified with FGFR1 as part of a focal amplification at 8p11.23.

Alterations observed in the corpus

• Co-amplified with FGFR1 at 8p11.23 in ~8% of primary prostate cancer (PRAD) in the TCGA cohort PMID:26544944
• Focal amplification at FGFR1/WHSC1L1 locus identified as an expanded Ras/Raf/RTK pathway driver in lung adenocarcinoma (LUAD) in the TCGA Pan-Lung study of 1,144 NSCLC cases; raises the proportion of lung ADCs with a candidate RTK pathway driver PMID:27158780.

Cancer types (linked)

• PRAD: Focal co-amplification with FGFR1 at 8p11.23 in ~8% of primary prostate tumors PMID:26544944
• LUAD: FGFR1/WHSC1L1 focal amplification identified as an expanded RTK pathway driver, contributing to the 76% of lung ADCs with a candidate Ras/Raf/RTK driver PMID:27158780.

Co-occurrence and mutual exclusivity

• Co-amplified with FGFR1 at 8p11.23 (recurrent focal amplification locus) PMID:26544944

Therapeutic relevance

Open questions

• The relative contributions of WHSC1L1 (NSD3) versus FGFR1 to the oncogenic phenotype driven by 8p11.23 amplification in prostate cancer have not been dissected.

Sources

• PMID:26544944

• PMID:27158780

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