The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type
<p>Abstract</p> <p>Background</p> <p><it>PIK3CA </it>is one of the genes most frequently mutated in human cancers and it is a potential target for personalized therapy. The aim of this study was to assess the frequency and type of <it>PIK3CA </it>...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-04-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Online Access: | http://www.jeccr.com/content/29/1/32 |
| _version_ | 1818142756900438016 |
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| author | Mattuzzi Silvia Lamba Simona Bersani Samantha De Manzoni Giovanni Cataldo Ivana Barbi Stefano Bardelli Alberto Scarpa Aldo |
| author_facet | Mattuzzi Silvia Lamba Simona Bersani Samantha De Manzoni Giovanni Cataldo Ivana Barbi Stefano Bardelli Alberto Scarpa Aldo |
| author_sort | Mattuzzi Silvia |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p><it>PIK3CA </it>is one of the genes most frequently mutated in human cancers and it is a potential target for personalized therapy. The aim of this study was to assess the frequency and type of <it>PIK3CA </it>mutations in gastric carcinoma and compare them with their clinical pathological correlates.</p> <p>Methods</p> <p>We analysed 264 gastric cancers, including 39 with microsatellite instability (MSI), for mutations in the two <it>PIK3CA </it>hotspots in exons 9 and 20 by direct sequencing of DNA obtained from microdissected cancer cells.</p> <p>Results</p> <p>The cases harbouring mutations were 42 (16%). All were heterozygous missense single base substitutions; the most common was H1047R (26/42; 62%) in exon 20 and the second was Q546K (4/42; 9.5%) in exon 9. All the mutated MSI cases (8/39) carried the H1047R mutation. No other association between <it>PI3KCA </it>mutations and their clinical pathological covariates was found. A metanalysis of the mutations occurring in the same regions presented in 27 publications showed that ratio between exon 20 and exon 9 prevalences was 0.6 (95% CI: 0.5 -0.8) for colon, 1.6 (95% CI: 1.1 -2.3) for breast, 2.7 (95% CI: 1.6 -4.9) for gastric and 4.1 (95% CI: 1.9 -10.3) for endometrial cancer.</p> <p>Conclusions</p> <p>The overall prevalence of <it>PIK3CA </it>mutations implies an important role for <it>PIK3CA </it>in gastric cancer. The lack of association with any clinical-pathological condition suggests that mutations in <it>PIK3CA </it>occur early in the development of cancer. The metanalysis showed that exon-selectivity is an important signature of cancer type reflecting different contexts in which tumours arise.</p> |
| first_indexed | 2024-12-11T11:20:50Z |
| format | Article |
| id | doaj.art-fe857c7b903c4134b6cd1deaf581f98f |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-11T11:20:50Z |
| publishDate | 2010-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-fe857c7b903c4134b6cd1deaf581f98f2022-12-22T01:09:10ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662010-04-012913210.1186/1756-9966-29-32The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer typeMattuzzi SilviaLamba SimonaBersani SamanthaDe Manzoni GiovanniCataldo IvanaBarbi StefanoBardelli AlbertoScarpa Aldo<p>Abstract</p> <p>Background</p> <p><it>PIK3CA </it>is one of the genes most frequently mutated in human cancers and it is a potential target for personalized therapy. The aim of this study was to assess the frequency and type of <it>PIK3CA </it>mutations in gastric carcinoma and compare them with their clinical pathological correlates.</p> <p>Methods</p> <p>We analysed 264 gastric cancers, including 39 with microsatellite instability (MSI), for mutations in the two <it>PIK3CA </it>hotspots in exons 9 and 20 by direct sequencing of DNA obtained from microdissected cancer cells.</p> <p>Results</p> <p>The cases harbouring mutations were 42 (16%). All were heterozygous missense single base substitutions; the most common was H1047R (26/42; 62%) in exon 20 and the second was Q546K (4/42; 9.5%) in exon 9. All the mutated MSI cases (8/39) carried the H1047R mutation. No other association between <it>PI3KCA </it>mutations and their clinical pathological covariates was found. A metanalysis of the mutations occurring in the same regions presented in 27 publications showed that ratio between exon 20 and exon 9 prevalences was 0.6 (95% CI: 0.5 -0.8) for colon, 1.6 (95% CI: 1.1 -2.3) for breast, 2.7 (95% CI: 1.6 -4.9) for gastric and 4.1 (95% CI: 1.9 -10.3) for endometrial cancer.</p> <p>Conclusions</p> <p>The overall prevalence of <it>PIK3CA </it>mutations implies an important role for <it>PIK3CA </it>in gastric cancer. The lack of association with any clinical-pathological condition suggests that mutations in <it>PIK3CA </it>occur early in the development of cancer. The metanalysis showed that exon-selectivity is an important signature of cancer type reflecting different contexts in which tumours arise.</p>http://www.jeccr.com/content/29/1/32 |
| spellingShingle | Mattuzzi Silvia Lamba Simona Bersani Samantha De Manzoni Giovanni Cataldo Ivana Barbi Stefano Bardelli Alberto Scarpa Aldo The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type Journal of Experimental & Clinical Cancer Research |
| title | The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type |
| title_full | The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type |
| title_fullStr | The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type |
| title_full_unstemmed | The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type |
| title_short | The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type |
| title_sort | analysis of pik3ca mutations in gastric carcinoma and metanalysis of literature suggest that exon selectivity is a signature of cancer type |
| url | http://www.jeccr.com/content/29/1/32 |
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