Epidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported. Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer types obtained by differential expression meta-analysis. Four cancer types (brain, thyroid, kidney, and pancreatic cancers) presented a significant overlap in gene expression deregulations in the same direction as ASD whereas two cancer types (lung and prostate cancers) showed differential expression profiles significantly deregulated in the opposite direction from ASD. Functional enrichment and LINCS L1000 based drug set enrichment analyses revealed the implication of several biological processes and pathways that were affected jointly in both diseases, including impairments of the immune system, and impairments in oxidative phosphorylation and ATP synthesis among others. Our data also suggest that brain and kidney cancer have patterns of transcriptomic dysregulation in the PI3K/AKT/MTOR axis that are similar to those found in ASD. These shared transcriptomic alterations could help explain epidemiological observations suggesting direct and inverse comorbid associations between ASD and particular cancer types.
CTCs)) and tumour biopsy samples. Results: The median age of pts was 56 (range 32-75). 48% (33/68) were colon tumours, 34% (23/68) rectal, 9% (6/68) rectosigmoid and 7% (5/68) small bowel. Pts had failed an average of 3 lines (range 1-5) of treatment prior to recruitment. 74% (50/68) of patients had both sufficient tumour DNA in their plasma, and archival biopsies for analysis. Sequencing of ctDNA detected all mutations reported in tumour in 76% (38/ 50) of pts. ctDNA analysis picked up additional mutations in 30% (15/50) of pts. The interval between collection of archival biopsies and blood tests (p ¼ 0.300) did not affect detection of new mutations. 31% (6/19) of pts treated with anti-EGFR therapy developed recognised resistance mutations (KRAS and EGFR) in ctDNA on serial analysis. The most commonly detected mutations were TP53 (60%), KRAS (51%), PIK3CA (15%) and PTEN (3%). Other mutated genes included CTNNB1, BRAF, FGFR3 and ERRB2. Pre-clinical models (organoids and patient-derived xenografts (PDX)) were attempted from blood (CTCs) and/or tumour tissue in 29% (20/68) of pts. CTC organoid cultures were optimised and successful in 1/17 pts. Conclusions: ctDNA may be used for routine molecular characterisation of metastatic SBC/CRC and results can be analysed to track the development of resistance.
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