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The genomic landscape of cutaneous #SCC reveals drivers and a novel #azathioprine associated mutational signature
https://www.nature.com/articles/s41467-018-06027-1#ref-CR53
Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies.
We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression.
Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets.
The genomic landscape of cutaneous #SCC reveals drivers and a novel #azathioprine associated mutational signature
https://www.nature.com/articles/s41467-018-06027-1#ref-CR53
Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies.
We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression.
Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets.
Nature Communications
The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature
Nature Communications - It is known cutaneous squamous cell carcinoma (cSCC) involves a high tumour mutation burden. Here the authors identify common cSCC mutated genes, copy number changes,...
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Association between use of #azathioprine and risk of acute #pancreatitis in children with inflammatory bowel disease: a Swedish–Danish nationwide cohort study
https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30401-2/fulltext
Studies have shown an association between use of azathioprine and increased risk of acute pancreatitis in adult inflammatory bowel disease. However, whether an association exists among paediatric patients is not known.
Within the first 90 days following initiation of azathioprine, 40 acute pancreatitis events occurred (incidence rate 49·1 events per 1000 person-years) compared with six events in the no-use group (8·4 events per 1000 person-years). Azathioprine use was associated with an increased risk of acute pancreatitis (incidence rate ratio 5·82 [95% CI 2·47–13·72]; absolute difference 1·0 [95% CI 0·3–2·6] events per 100 patients) during the 90-day risk period.
Interpretation
Use of azathioprine was associated with an increased risk of acute pancreatitis in children with inflammatory bowel disease during the first 90 days following treatment initiation, suggesting the need for regular and rigorous monitoring. The risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategies
Association between use of #azathioprine and risk of acute #pancreatitis in children with inflammatory bowel disease: a Swedish–Danish nationwide cohort study
https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30401-2/fulltext
Studies have shown an association between use of azathioprine and increased risk of acute pancreatitis in adult inflammatory bowel disease. However, whether an association exists among paediatric patients is not known.
Within the first 90 days following initiation of azathioprine, 40 acute pancreatitis events occurred (incidence rate 49·1 events per 1000 person-years) compared with six events in the no-use group (8·4 events per 1000 person-years). Azathioprine use was associated with an increased risk of acute pancreatitis (incidence rate ratio 5·82 [95% CI 2·47–13·72]; absolute difference 1·0 [95% CI 0·3–2·6] events per 100 patients) during the 90-day risk period.
Interpretation
Use of azathioprine was associated with an increased risk of acute pancreatitis in children with inflammatory bowel disease during the first 90 days following treatment initiation, suggesting the need for regular and rigorous monitoring. The risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategies