The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences
We have investigated microsatellite instability (MSI) in colorectal, gastric, endometrial and ovarian cancer as a result of mismatch repair (MMR) deficiency. We detected frameshift mutations in several genes that carry short repeated sequences and are important in cell fidelity and growth control; h...
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ftskemman:oai:skemman.is:1946/21561 2023-05-15T16:47:31+02:00 The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences Sigurður Ingvarsson 1956- Jónína Þuríður Jóhannsdóttir 1969- Jón Gunnlaugur Jónasson 1956- Jón Þór Bergþórsson 1966- Laufey Þóra Ámundadóttir 1962- Guðríður H. Ólafsdóttir 1954- Jónas Björn Magnússon 1952- Valgarður Egilsson 1940- Háskóli Íslands 2000-01 application/pdf http://hdl.handle.net/1946/21561 en eng http://www.spandidos-publications.com/ijo/16/1/133 http://www.ncbi.nlm.nih.gov/pubmed/10601558 https://www.researchgate.net/publication/12698990_The_effect_of_mismatch_repair_deficiency_on_tumourigenesis_microsatellite_instability_affecting_genes_containing_short_repeated_sequences International Journal of Oncology, 2000, 16, 133-139 1019-6439 http://hdl.handle.net/1946/21561 Article 2000 ftskemman 2022-12-11T06:53:36Z We have investigated microsatellite instability (MSI) in colorectal, gastric, endometrial and ovarian cancer as a result of mismatch repair (MMR) deficiency. We detected frameshift mutations in several genes that carry short repeated sequences and are important in cell fidelity and growth control; hMSH3, hMSH6, BAX, IGFIIR, TGFbetaIIR, E2F4 and BRCA2. Accumulation of mutations was heterogeneous and mainly restricted to tumours showing MSI at several loci (MSI-H). Both insertions and deletions were evident and occasional intratumour heterogeneity was evident with more than one different additional allele in the tumour. Most MSI-H tumours had acquired mutations in more than one gene and longer repeated sequences were more frequently targets for mutations. The TGFbetaIIR gene was mutated in 62%, the hMSH3 gene in 43%, the E2F4 gene in 35%, the hMSH6 in 32%, the BAX gene in 32%, the IGFIIR gene in 26%, and the BRCA2 gene in 2% of the MSI-H tumours. Homozygous mutations or mutation of both alleles were evident in all genes except BRCA2, in total 23/105 mutated cases, varying from 7% for BAX to 50% for E2F4. E2F4 mutations were exclusively found in colon tumours and E2F4 polymorphisms was found in 8% of cases. No difference in mutation prevalence was noted between cancer types apart from TGFbetaIIR mutations, which were frequently found in colon and gastric tumours but not in endometrial tumours, suggesting that endometrial tumours progress by a different route where TGFbetaIIR mutations are less favourable. This work was financially supported by the Research Council of Iceland, the Icelandic Cancer Society, the University of Iceland Graduate Research fund, the Memorial Fund og Bergthora Magnusdottir and Jakob B. Bjarnason and the Science Fund of the University Hospital of Iceland. Article in Journal/Newspaper Iceland Skemman (Iceland) |
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We have investigated microsatellite instability (MSI) in colorectal, gastric, endometrial and ovarian cancer as a result of mismatch repair (MMR) deficiency. We detected frameshift mutations in several genes that carry short repeated sequences and are important in cell fidelity and growth control; hMSH3, hMSH6, BAX, IGFIIR, TGFbetaIIR, E2F4 and BRCA2. Accumulation of mutations was heterogeneous and mainly restricted to tumours showing MSI at several loci (MSI-H). Both insertions and deletions were evident and occasional intratumour heterogeneity was evident with more than one different additional allele in the tumour. Most MSI-H tumours had acquired mutations in more than one gene and longer repeated sequences were more frequently targets for mutations. The TGFbetaIIR gene was mutated in 62%, the hMSH3 gene in 43%, the E2F4 gene in 35%, the hMSH6 in 32%, the BAX gene in 32%, the IGFIIR gene in 26%, and the BRCA2 gene in 2% of the MSI-H tumours. Homozygous mutations or mutation of both alleles were evident in all genes except BRCA2, in total 23/105 mutated cases, varying from 7% for BAX to 50% for E2F4. E2F4 mutations were exclusively found in colon tumours and E2F4 polymorphisms was found in 8% of cases. No difference in mutation prevalence was noted between cancer types apart from TGFbetaIIR mutations, which were frequently found in colon and gastric tumours but not in endometrial tumours, suggesting that endometrial tumours progress by a different route where TGFbetaIIR mutations are less favourable. This work was financially supported by the Research Council of Iceland, the Icelandic Cancer Society, the University of Iceland Graduate Research fund, the Memorial Fund og Bergthora Magnusdottir and Jakob B. Bjarnason and the Science Fund of the University Hospital of Iceland. |
author2 |
Háskóli Íslands |
format |
Article in Journal/Newspaper |
author |
Sigurður Ingvarsson 1956- Jónína Þuríður Jóhannsdóttir 1969- Jón Gunnlaugur Jónasson 1956- Jón Þór Bergþórsson 1966- Laufey Þóra Ámundadóttir 1962- Guðríður H. Ólafsdóttir 1954- Jónas Björn Magnússon 1952- Valgarður Egilsson 1940- |
spellingShingle |
Sigurður Ingvarsson 1956- Jónína Þuríður Jóhannsdóttir 1969- Jón Gunnlaugur Jónasson 1956- Jón Þór Bergþórsson 1966- Laufey Þóra Ámundadóttir 1962- Guðríður H. Ólafsdóttir 1954- Jónas Björn Magnússon 1952- Valgarður Egilsson 1940- The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences |
author_facet |
Sigurður Ingvarsson 1956- Jónína Þuríður Jóhannsdóttir 1969- Jón Gunnlaugur Jónasson 1956- Jón Þór Bergþórsson 1966- Laufey Þóra Ámundadóttir 1962- Guðríður H. Ólafsdóttir 1954- Jónas Björn Magnússon 1952- Valgarður Egilsson 1940- |
author_sort |
Sigurður Ingvarsson 1956- |
title |
The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences |
title_short |
The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences |
title_full |
The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences |
title_fullStr |
The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences |
title_full_unstemmed |
The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences |
title_sort |
effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences |
publishDate |
2000 |
url |
http://hdl.handle.net/1946/21561 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://www.spandidos-publications.com/ijo/16/1/133 http://www.ncbi.nlm.nih.gov/pubmed/10601558 https://www.researchgate.net/publication/12698990_The_effect_of_mismatch_repair_deficiency_on_tumourigenesis_microsatellite_instability_affecting_genes_containing_short_repeated_sequences International Journal of Oncology, 2000, 16, 133-139 1019-6439 http://hdl.handle.net/1946/21561 |
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1766037608332263424 |