Thomas J Hudson’s research while affiliated with Ontario Institute for Cancer Research and other places

... * Beifang Yang beifangy2016@163.com a growing body of evidence has suggested that inherited susceptibility is also a major component of colorectal cancer predisposition, with an estimated 12-35% risk attributed to genetic factors (Chang et al. 2018;Gong et al. 2018b). Advancements in global genomic research have led to the identification of more than 200 risk loci associated with CRC through genome-wide association study (GWAS) (Chen et al. 2024;Fernandez-Rozadilla et al. 2023;Lu et al. 2019). However, the majority of GWAS-identified single nucleotide polymorphisms (SNPs) often span large regions due to linkage disequilibrium (LD) and can act over long distances, leading to a formidable challenge for delineating the causal variants and their target genes related to cancer development. ...

Reference:

Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development

... In all genetic (sub)classes of CRCs, mutations related to SBS88, which is linked to bacterial infections with colibactin-producing bacteria [14,44,45], can be identified. This can be observed with a high probability along with the co-occurrence of MMRd SBS44, as reported in large datasets of CRC [37,46]. ...

Reference:

Mutational Signatures in Colorectal Cancer: Translational Insights, Clinical Applications, and Limitations

... Even though individuals with a personal or family history of colorectal neoplasia, in ammatory bowel disease, or hereditary forms of CRC are prone to developing polyps, 75-95% of all colon cancers develop in individuals with little or no genetic predisposition for malignancy. 2 Additionally, early-stage CRC is mostly asymptomatic, and many patients are diagnosed at advanced stages. 1,2 Moreover, it is well-known that if colorectal cancer is detected in early stage, it is curable. ...

Reference:

Virtual Colonoscopy: Clinical Advances and Practical Challenges

... We ran the SIGNAL webtool (https://signal.mutationalsignatures.com/) (Degasperi et al. 2020) under default parameters to identify the single base substitution (SBS) signatures active in each patient (Alexandrov et al. 2020). As recommended by the authors, SBS fitting was performed using candidate SBS signatures from CRC. ...

Reference:

Genomic diversity and BCL9L mutational status in CTC pools predict overall survival in metastatic colorectal cancer

... In clinical practice, differentiating between multiple primary lung cancers and intrapulmonary metastasis is challenging using pathology or morphologic appearance alone, and NGS is now recommended to help definitively differentiate these entities [5,[8][9][10][11][12][13][14][15]. When using genomic results to define multiple primaries versus intrapulmonary metastasis, we observed significantly improved survival in those with genome-defined multiple primaries versus intrapulmonary metastasis. ...

Reference:

Repeat Next-Generation Sequencing (15-Gene Panel) in Unifocal, Synchronous, and Metachronous Non-Small-Cell Lung Cancer—A Single-Center Experience

... Characterizing the full spectrum of SVs in human genomes makes it possible to understand the distribution of SVs in different populations [8]. Additionally, SVs have been found to play a critical role in the development of certain diseases, such as cancer [22] and Alzheimer's [36]. SVs are typically referred to any genome sequence altering event, except for deletions or insertions (indels) shorter than 50 bp [32]. ...

Reference:

Blackbird: structural variant detection using synthetic and low-coverage long-reads

... RPL39L is a recently evolved ( 1 ) and non-redundant paralog of RPL39L that has just been implicated in the translation of long-lived, sperm cell-specific proteins ( 11 ). However, the RPL39L mRNA was also observed outside of the germ cell lineage, particularly in ovarian ( 12 ) and breast cancer tissues ( 2 ), as well as in lung cancer ( 13 ) and neuroblastoma ( 11 ) cell lines, where the expression appears to be driven by gene amplifications ( 14 ) and CpG island hypomethylation ( 13 ). These observations suggest that RPL39L's function extends beyond the translation of long-lived sperm cell proteins. ...

Reference:

Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains

... Modifiable risk factors contribute significantly to predictive discrimination for ovarian, breast, lung, pancreatic, and esophageal cancers, which aligns with their strong associations with these cancer types [31]. Including PRSs substantially enhances predictive discrimination for colorectal and breast cancers, in line with the wealth of genetic data available for these cancers in East Asian populations [32,33]. Although our study revealed a strong association between PRS and prostate cancer, the improvement in prediction performance was much weaker than that in European populations, likely due to differences in baseline model performance between Chinese populations (C-index of 0.868) and European populations (C-index of 0.716) [34]. ...

Reference:

Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank

... Genomic alterations have been ranked based on their recurrence and on their functional consequences, finally developing a clustering methodology to discriminate between potential driver events [46]. The extension of the sequencing to intergenic regions allowed evaluation of the burden of putative driver mutations in noncoding regions: on the pan-cancer database, 13% of all mutations were represented by driver point-mutation events in an intergenic region, with 25% of all PCAWG cancers analysed bearing at least one, one-third of which occurred in the TERT promoter, confirming its role in cancer [73][74][75][76][77][78][79]. On the counterpart, 91% of all cancers harboured a somatic driver event in a coding region of a gene (Fig. 3). ...

Reference:

Global mapping of cancers: The Cancer Genome Atlas and beyond

... As the tumor progresses, altered metabolism, and aberrant vasculature leads to generation of hypoxic niches [1,2]. Hypoxia is a well-known orchestrator of genetic [3,4] and epigenetic alterations [5,6] and is considered to be an important hallmark of the TME that promotes epithelial to mesenchymal transition (EMT) [7,8], cancer invasion [9], stemness [10] and drug resistance [11]. Hypoxia-inducible factor 1-alpha (HIF1α), the master transcription factor of hypoxia, empirically facilitates the transcription of major genes in response to the hypoxic stress [12]. ...

Reference:

Hypoxia-induced ATF3 escalates breast cancer invasion by increasing collagen deposition via P4HA1