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BackgroundMucinous differentiation occurs in 5–15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta-analytical techniques to clarify the molecular associations of mucinous colorectal cancer.MethodsThis study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non-mucinous colorectal adenocarcinoma. A random-effects model was used for analysis.ResultsData from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1·46, 95 per cent c.i. 1·08 to 2·00, P = 0·014) and BRAF (OR 3·49, 2·50 to 4·87; P < 0·001) mutation, MSI (OR 3·98, 3·30 to 4·79; P < 0·001) and CIMP (OR 3·56, 2·85 to 4·43; P < 0·001), and negatively with altered p53 expression (OR 0·46, 0·31 to 0·67; P < 0·001).ConclusionThe genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.

Introduction Mucinous adenocarcinoma (MA) of the rectum accounts for 5-15% of rectal cancers. This histological subtype has been shown to have a worse response to chemoradiotherapy and worse long term outcomes when compared to non-mucinous adenocarcinoma (NMA). The aim of this study was to compare the genomic landscape of rectal MA to rectal NMA. Method Using the BGISEQ PE100 platform, paired end whole genome sequencing was carried out on tumour and matched normal tissue from cases of MA. The Cancer Genome Atlas was interrogated to identify further cases of rectal MA and cases of rectal NMA with sequencing data that could be used as a control group. In-depth bioinformatic analysis was undertaken and the genomic landscapes of the two subtypes were compared. Result A total of 14 cases of MA were compared to 74 cases of NMA. The microsatellite instability-high rate in the MA group was 14.29% vs 4.05% in the NMA group. POLE mutations were found in 5.41% of the NMA group compared to 0.00% of the MA group. KRAS, BRAF and PIK3CA mutations were more frequent in the MA group whereas TP53 and APC mutations were more common in the NMA group. Significant differences between the groups were identified in the most frequently mutated genes. Copy number alteration, mutational signatures, structural variation and microbiome findings will also be described. Conclusion MA of the rectum is not just phenotypically distinct, it is a distinct genotype. This could have implications when considering neoadjuvant and adjuvant treatment strategies in the future. Take-home message Mucinous adenocarcinoma differs from a genomic perspective from non-mucinous adenocarcinoma and this may have implications for treatment strategies in the future

Introduction The incidence of brain metastases is increasing despite longer survival rates for patients with advanced breast cancer. The identification of novel therapeutic targets for these patients is an urgent unmet clinical need. Sequencing of metastatic tumours have largely focused on mutations however gene fusions have an important, yet underappreciated role in tumorigenesis and disease progression. In this study, we investigate the role of gene fusions in brain metastatic disease and their impact on altered therapeutic responses. Method RNA sequencing was performed on the largest reported cohort of patient matched primary and resected brain metastatic tumours (45 patients n=90 samples). Expressed gene fusions were detected computationally using STAR-Fusion and Arriba. Result We identified differential gene fusion burden in brain metastatic tumours (medium of 58) vs. primary breast tumours (medium of 38) (p Conclusion These results highlight the significant role of gene fusions in breast cancer brain metastases. Abbreviations MAPK Mitogen Activated Protein Kinase, HER Human Epidermal Receptor, CDK12 Cyclin Dependent Kinase 12 Take-home message We highlight the significant role of gene fusions in breast cancer brain metastases and offer specific actionable genomic alterations to be exploited.