The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer

Malander, Susanne; Rambech, Eva; Kristoffersson, Ulf; Halvarsson, Britta; Ridderheim, Mona; Borg, Åke; Nilbert, Mef

doi:10.1016/j.ygyno.2005.10.029

Cited by 119 publications

(102 citation statements)

References 34 publications

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“…Several exon deletions have recurrently been identified with e.g. the deletions of exon 16 and exons 17-19 in MLH1 recognized in the UK and in Sweden and the deletion of exons 1-6 in MSH2 as an American founder mutation [16,27,31,32]. A deletion of exons 1-2 in MSH2 was found in four families from northern Jutland and southern Sealand.…”

Section: Discussionmentioning

confidence: 99%

Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population

et al. 2008

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An increasing number of mismatch-repair (MMR) gene mutations have been identified in hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome. This study presents the population-based Danish MMR gene mutation profile, which contains 138 different MMR gene alterations. Among these, 88 mutations in 164 families are considered pathogenic and an additional 50 variants from 76 families are considered to represent variants of unknown pathogenicity. The different MMR genes contribute to 40% (MSH2), 29% (MLH1), and 22% (MSH6) of the mutations and the Danish population thus shows a considerably higher frequency of MSH6 mutations than previously described. Although 69/88 (78%) pathogenic mutations were present in a single family, previously recognized recurrent/founder mutations were causative in 75/137 (55%) MLH1/MSH2 mutant families. In addition, the Danish MLH1 founder mutation c.1667+2_1667_+8TAAATCAdelinsATTT was identified in 14/58 (24%) MLH1 mutant families. The Danish Lynch syndrome population thus demonstrates that MSH6 mutations and recurrent/founder mutations have a larger contribution than previously recognized, which implies that the MSH6 gene should be included in routine diagnostics and suggests that directed analysis of recurrent/founder mutations may be feasible e.g. in families were diagnostic material is restricted to archival tissue.

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Section: Discussionmentioning

confidence: 99%

Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population

et al. 2008

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“…4 -7 It is estimated that at least 10% of all epithelial ovarian cancers are hereditary, with the BRCA genes contributing to at least 90% of these cases and small percentages attributable to other genes, like HNPCC 39 and perhaps a yet to be discovered susceptibility gene. 8 As germline BRCA1/2 mutations are relatively uncommon among patients with ovarian cancer in the general population, it is very important to identify risk factors that can predict the likelihood of finding these mutations to identify mutation carriers.…”

Section: Discussionmentioning

confidence: 99%

Prediction of BRCA1/2 mutation status in patients with ovarian cancer from a hospital-based cohort

Jacobi

Ierland

Asperen

et al. 2007

Genetics in Medicine

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Purpose: To describe patient, tumor, and family histories of cancer in a hospital-based cohort of patients with ovarian cancer and to identify the predictive value of these characteristics for (non)carrying a BRCA1 or BRCA2 mutation. Methods: Women diagnosed with invasive ovarian cancer between 1999 and 2003 in the west region of The Netherlands and unselected for age at diagnosis or cancer family history were included. Information was gathered on patient and tumor characteristics; p53; HER-2/neu, and KI-67 protein-expression; BRCA1/2 mutations; and family histories of cancer. Prediction tests were constructed using multivariate analyses. Results: Our study included 85 women (mean age at diagnosis, 57.6 years; standard deviation, 11.0 years). Six of these women had been previously or concurrently diagnosed with another tumor. Of the ovarian cancers, 41 (48.2%) were in an early stage (FIGO I or II). Five pathogenic mutations (6.1%) and six unclassified variants (7.3%) were identified in BRCA1/2; when the total sensitivity of the mutation scanning was taken into account, it was estimated to reflect seven pathogenic mutations (8.5%) and eight unclassified variants (9.8%). Sixty-nine women (81.2%) had at least one relative with cancer. A personal history of breast cancer and a family history of breast, ovarian, or uterine/ endometrioid cancer were found to predict the presence of pathogenic mutations. Conclusion: As the combination of a personal history of breast cancer and a family history of breast, ovarian, or uterine/endometrioid cancer had good predictive value for the presence of a pathogenic BRCA1/2 mutation, the presented prediction test is a useful instrument to identify those women eligible for DNA testing. Genet Med 2007:9(3):173-179.

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“…The median age at diagnosis was 60 years in the sporadic subset, 57 years in the BRCA1 subset and 47 years in the HNPCC subset. The 24 sporadic tumors were obtained from a population based consecutive series of ovarian cancers, in which mutations in BRCA1 and BRCA2 had been excluded through mutation analysis and retained MMR function had been demonstrated using immunostaining against the MLH1, PMS2, MSH2 and MSH6 proteins (13,14). All BRCA1 mutations were classified as disease predisposing and were available from a population based consecutive series of ovarian cancers.…”

Section: Methodsmentioning

confidence: 99%

Genetic profiles distinguish different types of hereditary ovarian cancer

Domanska¹

2010

Oncol Rep

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Abstract. Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers as a control group. Unsupervised cluster analysis identified two distinct subgroups related to genetic complexity. Sporadic and HBOC associated tumors had complex genetic profiles with an average 41% of the genome altered, whereas the mismatch repair defective tumors had stable genetic profiles, with an average 18% of the genome altered. Losses of 4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset. Discriminating genes within these regions include BRCA2, FOXO1A and RB1. Gains on chromosomes 17 and 19 characterized the HNPCC tumors, but target genes herein are unknown. The results indicate that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer.

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The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer

Cited by 119 publications

References 34 publications

Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population

Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population

Prediction of BRCA1/2 mutation status in patients with ovarian cancer from a hospital-based cohort

Genetic profiles distinguish different types of hereditary ovarian cancer

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