Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer prevalent in Southern China and Southeast Asia. The current knowledge on the molecular pathogenesis of NPC is still inadequate to improve disease management. Using gene expression microarrays, we have identified the four-jointed box 1 (FJX1) gene to be upregulated in primary NPC tissues relative to nonmalignant tissues. An orthologue of human FJX1, the four-jointed (fj) gene in Drosophila and Fjx1 in mouse, has reported to be associated with cancer progression pathways. However, the exact function of FJX1 in human is not well characterized. The overexpression of FJX1 mRNA was validated in primary NPC tissue samples, and the level of FJX1 protein was significantly higher in a subset of NPC tissues (42%) compared to the normal epithelium, where no expression of FJX1 was observed (p = 0.01). FJX1 is also found to be overexpressed in microarray datasets and TCGA datasets of other cancers including head and neck cancer, colorectal, and ovarian cancer. Both siRNA knockdown and overexpression experiments in NPC cell lines showed that FJX1 promotes cell proliferation, anchorage-dependent growth, and cellular invasion. Cyclin D1 and E1 mRNA levels were increased following FJX1 expression indicating that FJX1 enhances proliferation by regulating key proteins governing the cell cycle. Our data suggest that the overexpression of FJX1 contributes to a more aggressive phenotype of NPC cells and further investigations into FJX1 as a potential therapeutic target for NPC are warranted. The evaluation of FJX1 as an immunotherapy target for NPC and other cancers is currently ongoing.
Rare protein-truncating variants (PTVs) in PALB2 confer increased risk to breast cancer, but relatively few studies have reported the characteristics of tumours with PALB2 PTVs. In this study, we describe molecular characteristics of tumours with either germline or somatic alterations in PALB2. DNA from fresh frozen tumour tissues and matched peripheral blood lymphocytes for 560 breast cancer patients was subjected for whole-exome sequencing (WES), and RNA from tumour tissues was subjected to RNA sequencing (RNA-seq). We found six cases with germline and three with somatic protein-truncating variants in PALB2. The characteristics of tumours in patients with PALB2 PTVs were similar to those with BRCA1 and BRCA2 PTVs, having significantly more somatic alterations, and a high proportion of the mutational signature and genomic scar scores characteristic of deficiencies in homologous recombination (HR), compared to tumours arising in non-carriers. Unlike tumours arising in patients with BRCA1 and BRCA2 PTVs, PALB2 tumours did not have high prevalence of TP53 somatic alterations or an enriched immune microenvironment. In summary, PALB2 tumours show the homologous recombination deficiencies characteristic of BRCA1 and BRCA2 tumours, and highlight the potential clinical relevance of PALB2 mutational status in guiding therapeutic choices.