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New gene mutations identified in bladder cancer
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Four genetic variants associated with an increased risk of developing oesphageal cancer and precancerous Barrett’s oesophagus have been identified in an international study published in Nature Genetics. Although several lifestyle factors such as smoking and poor diet have been blamed for a recent surge in the number of patients with oesphageal cancer, researchers have long suspected that genetics could also play a part. Vaughan and coworkers compared DNA and lifestyle risk-exposure data from 2390 individuals with oesophageal adenocarcinoma, 3175 individuals who had Barrett’s oesphagus, and a control group of 10 120 individuals. Genetic variants that were significantly associated with oesophageal adenocarcinoma and Barrett’s oesophagus were identified on chromosomes 3 (near FOXP1), 9
(BARX1), and 19 (CRCT1). The most significant of the three variants was on chromosome 19 (CRCT1) at position rs10419226 (odds ratio 1·18, 95% CI 1·12–1·24). A location on chromosome 16 chromosome 16 (near FOXF1) that had been previously linked with Barrett’s oesophagus was confirmed to be associated with the risk of oesophageal cancer. Genetic influence on susceptibility to cancer was stronger in the early stages of Barrett’s oesophagus development rather than in the progression of Barrett’s oesophagus to cancer. Len Lichtenfeld, Deputy Chief Medical Officer for the American Cancer Society (GA, USA), commented: “This study may help gives us clues as to whether someone has a susceptibility to oesophageal cancer, which could allow for
lifestyle changes to lower the risk of developing the cancer. There is still some way to go before this work translates into diagnostic and therapeutic methods, but it’s exciting to be in this position.” Tim Underwood, an oesophageal surgeon and researcher at the University of Southampton (UK), said: “A number of research projects are currently…updating our understanding of the genetic landscape of oesophageal cancer, and this study adds to that understanding. It’s timely given that oesophageal cancer is the fastest rising cancer in men in the UK. The study suggests that the genetic predisposition to the cancer is established at the same time as Barrett’s oesophagus, and gives us new genetic targets that will need to be unpicked with future research.”
ISM/Science Photo Library
Genetic variants linked to oesophageal cancer
Published Online October 18, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70484-4 For the study see Nat Genet 2013; published online Oct 13. DOI:10.1038/ng.2796
Sanjay Tanday
New gene mutations identified in bladder cancer Two studies published online in Nature Genetics highlight the prevalence of STAG2 mutations in urothelial bladder cancer (UBC). A team of researchers led by Francisco Real at the Spanish National Cancer Centre, Madrid, sequenced the exomes of 17 non-muscle-invasive bladder cancers (NMIBCs), followed by a prevalence screen of 60 tumours, mainly NMIBC. The investigators identified new mutations in genes involved in chromatin modification (MLL2, ASXL2, and BPTF), cell division (STAG2, SMC1A, and SMC1B), and DNA repair (ATM, ERCC2, and FANCA). STAG2, a cohesin subunit, was frequently mutated or lost in low-stage or low-grade UBC tumours; loss was associated with decreased disease progression and improved patient survival. Real said: “Most next-generation sequencing studies have uncovered
genes that are involved in a small subset of tumours. By contrast, in this study, STAG2 inactivation is involved in more than 30% of non-muscle invasive tumours, indicating that it is a major player in this cancer.” In a second study, led by Todd Waldman, Georgetown University, Washington, DC, USA, investigators screened 2214 tumours through immunohistochemistry using a STAG2 monoclonal antibody. 52 of 295 UBCs (18%) had complete loss of STAG2 expression. Sequence analysis of 111 primary UBCs showed STAG2 mutations in 36% of noninvasive papillary carcinomas, 27% of superficially invasive carcinomas, and 13% of PT2–PT4 muscle-invasive carcinomas. Waldmann said: “STAG2 immunohistochemistry is an extremely robust assay and STAG2 expression appears to be quite powerful as a biomarker.”
www.thelancet.com/oncology Vol 14 November 2013
James Catto, Sheffield University, UK, commented: “In clinical practice, STAG2 mutations could identify a cohort of low-risk noninvasive tumours suitable for lowintensity surveillance, which do not necessarily need adjuvant intravesical chemotherapy.” Previous studies of other tumours have suggested that STAG mutations act through the promotion of aneuploidy; however, Real noted: “The findings are completely concordant: STAG2 inactivation is more common in tumours without chromosomal changes, and in some cases, it occurs in tumours with a completely normal number of chromosomes. Our results, [and Waldman’s], strongly suggest that STAG2 acts through additional mechanisms, yet to be unraveled.”
Published Online October 18, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70485-6 For the study by Real and coworkers see Nat Genet 2013; published online Oct 13. DOI:10.1038/ng.2799 For the study by Waldman and coworkers see Nat Genet 2013; published online Oct 13. DOI:10.1038/ng.2800
Hilary Marshall e496
Four genetic variants associated with an increased risk of developing oesphageal cancer and precancerous Barrett’s oesophagus have been identified in an international study published in Nature Genetics. Although several lifestyle factors such as smoking and poor diet have been blamed for a recent surge in the number of patients with oesphageal cancer, researchers have long suspected that genetics could also play a part. Vaughan and coworkers compared DNA and lifestyle risk-exposure data from 2390 individuals with oesophageal adenocarcinoma, 3175 individuals who had Barrett’s oesphagus, and a control group of 10 120 individuals. Genetic variants that were significantly associated with oesophageal adenocarcinoma and Barrett’s oesophagus were identified on chromosomes 3 (near FOXP1), 9
(BARX1), and 19 (CRCT1). The most significant of the three variants was on chromosome 19 (CRCT1) at position rs10419226 (odds ratio 1·18, 95% CI 1·12–1·24). A location on chromosome 16 chromosome 16 (near FOXF1) that had been previously linked with Barrett’s oesophagus was confirmed to be associated with the risk of oesophageal cancer. Genetic influence on susceptibility to cancer was stronger in the early stages of Barrett’s oesophagus development rather than in the progression of Barrett’s oesophagus to cancer. Len Lichtenfeld, Deputy Chief Medical Officer for the American Cancer Society (GA, USA), commented: “This study may help gives us clues as to whether someone has a susceptibility to oesophageal cancer, which could allow for
lifestyle changes to lower the risk of developing the cancer. There is still some way to go before this work translates into diagnostic and therapeutic methods, but it’s exciting to be in this position.” Tim Underwood, an oesophageal surgeon and researcher at the University of Southampton (UK), said: “A number of research projects are currently…updating our understanding of the genetic landscape of oesophageal cancer, and this study adds to that understanding. It’s timely given that oesophageal cancer is the fastest rising cancer in men in the UK. The study suggests that the genetic predisposition to the cancer is established at the same time as Barrett’s oesophagus, and gives us new genetic targets that will need to be unpicked with future research.”
ISM/Science Photo Library
Genetic variants linked to oesophageal cancer
Published Online October 18, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70484-4 For the study see Nat Genet 2013; published online Oct 13. DOI:10.1038/ng.2796
Sanjay Tanday
New gene mutations identified in bladder cancer Two studies published online in Nature Genetics highlight the prevalence of STAG2 mutations in urothelial bladder cancer (UBC). A team of researchers led by Francisco Real at the Spanish National Cancer Centre, Madrid, sequenced the exomes of 17 non-muscle-invasive bladder cancers (NMIBCs), followed by a prevalence screen of 60 tumours, mainly NMIBC. The investigators identified new mutations in genes involved in chromatin modification (MLL2, ASXL2, and BPTF), cell division (STAG2, SMC1A, and SMC1B), and DNA repair (ATM, ERCC2, and FANCA). STAG2, a cohesin subunit, was frequently mutated or lost in low-stage or low-grade UBC tumours; loss was associated with decreased disease progression and improved patient survival. Real said: “Most next-generation sequencing studies have uncovered
genes that are involved in a small subset of tumours. By contrast, in this study, STAG2 inactivation is involved in more than 30% of non-muscle invasive tumours, indicating that it is a major player in this cancer.” In a second study, led by Todd Waldman, Georgetown University, Washington, DC, USA, investigators screened 2214 tumours through immunohistochemistry using a STAG2 monoclonal antibody. 52 of 295 UBCs (18%) had complete loss of STAG2 expression. Sequence analysis of 111 primary UBCs showed STAG2 mutations in 36% of noninvasive papillary carcinomas, 27% of superficially invasive carcinomas, and 13% of PT2–PT4 muscle-invasive carcinomas. Waldmann said: “STAG2 immunohistochemistry is an extremely robust assay and STAG2 expression appears to be quite powerful as a biomarker.”
www.thelancet.com/oncology Vol 14 November 2013
James Catto, Sheffield University, UK, commented: “In clinical practice, STAG2 mutations could identify a cohort of low-risk noninvasive tumours suitable for lowintensity surveillance, which do not necessarily need adjuvant intravesical chemotherapy.” Previous studies of other tumours have suggested that STAG mutations act through the promotion of aneuploidy; however, Real noted: “The findings are completely concordant: STAG2 inactivation is more common in tumours without chromosomal changes, and in some cases, it occurs in tumours with a completely normal number of chromosomes. Our results, [and Waldman’s], strongly suggest that STAG2 acts through additional mechanisms, yet to be unraveled.”
Published Online October 18, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70485-6 For the study by Real and coworkers see Nat Genet 2013; published online Oct 13. DOI:10.1038/ng.2799 For the study by Waldman and coworkers see Nat Genet 2013; published online Oct 13. DOI:10.1038/ng.2800
Hilary Marshall e496