Gabriela Möslein

HELIOS St. Josefs-Hospital Bochum-Linden, Bochum, North Rhine-Westphalia, Germany

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Publications (110)687.86 Total impact

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    ABSTRACT: Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus nonaspirin--mean 3.8 mm versus 5.5 mm for patients treated 1 or more years (adjusted P = 0.09) and mean 3.0 mm versus 6.0 mm for patients treated more than 1 year (P = 0.02); there were similar weaker trends with RS versus non-RS. Exploratory translational endpoints included crypt length (which was significantly shorter in normal-appearing mucosa in the RS group over time) and laboratory measures of proliferation (including Ki67). This clinical trial is the largest ever conducted in the setting of FAP and found a trend of reduced polyp load (number and size) with 600 mg of aspirin daily. RS had no clinical effect on adenomas.
    Cancer Prevention Research 05/2011; 4(5):655-65. DOI:10.1158/1940-6207.CAPR-11-0106 · 5.27 Impact Factor
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    ABSTRACT: The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP Integration and Implementation Meeting at UNESCO in Paris, to review the progress of this pilot program. A wide range of topics were covered, including issues relating to genotype-phenotype data submission to the InSiGHT Colon Cancer Gene Variant Databases (chromium.liacs.nl/LOVD2/colon_cancer/home.php). The meeting also canvassed the recent exciting developments in models to evaluate the pathogenicity of unclassified variants using in silico data, tumor pathology information, and functional assays, and made further plans for the future progress and sustainability of the pilot program.
    Human Mutation 04/2011; 32(4):491-4. DOI:10.1002/humu.21450 · 5.05 Impact Factor
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    ABSTRACT: Missense mutations of the DNA mismatch repair gene MLH1 are found in a significant fraction of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) and their pathogenicity often remains unclear. We report here all 88 MLH1 missense variants identified in families from the German HNPCC consortium with clinical details of these patients/families. We investigated 23 MLH1 missense variants by two functional in vivo assays in yeast; seven map to the ATPase and 16 to the protein interaction domain. In the yeast-2-hybrid (Y2H) assay three variants in the ATPase and twelve variants in the interaction domain showed no or a reduced interaction with PMS2; seven showed a normal and one a significantly higher interaction. Using the Lys2A (14) reporter system to study the dominant negative mutator effect (DNE), 16 variants showed no or a low mutator effect, suggesting that these are nonfunctional, three were intermediate and four wild type in this assay. The DNE and Y2H results were concordant for all variants in the interaction domain, whereas slightly divergent results were obtained for variants in the ATPase domain. Analysis of the stability of the missense proteins in yeast and human embryonic kidney cells (293T) revealed a very low expression for seven of the variants in yeast and for nine in human cells. In total 15 variants were classified as deleterious, five were classified as variants of unclassified significance (VUS) and three were basically normal in the functional assays, P603R, K618R, Q689R, suggesting that these are neutral.
    Familial Cancer 03/2011; 10(2):273-84. DOI:10.1007/s10689-011-9431-4 · 1.62 Impact Factor
  • Emanuel Burdzik, Daniel Quast, Gabriela Möslein
    Viszeralmedizin / Visceral Medicine 01/2011; 27(4):300-307. DOI:10.1159/000330787 · 0.10 Impact Factor
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    ABSTRACT: The third Human Variome Project (HVP) Meeting "Integration and Implementation" was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10-14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health. The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current framework of HVP activities: Ethics; Nomenclature and Standards; Publication, Credit and Incentives; Data Collection from Clinics; Overall Data Integration and Access-Peripheral Systems/Software; Data Collection from Laboratories; Assessment of Pathogenicity; Country Specific Collection; Translation to Healthcare and Personalized Medicine; Data Transfer, Databasing, and Curation; Overall Data Integration and Access-Central Systems; and Funding Mechanisms and Sustainability. In addition, three societies that support the goals and the mission of HVP also held their own Workshops with the view to advance disease-specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium.
    Human Mutation 12/2010; 31(12):1374-81. DOI:10.1002/humu.21379 · 5.05 Impact Factor
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    ABSTRACT: The study aimed to describe genetical and clinical features of attenuated familial adenomatous polyposis (AFAP) and to propose clinical criteria and guidelines for treatment and surveillance. A questionnaire study was carried out of polyposis registries with data on patients with presumed AFAP, defined as having ≤ 100 colorectal adenomas at age ≥ 25. One hundred and ninety-six patients were included. The median number of adenomas was 25 (0-100) with a uniform distribution of colorectal adenomas and carcinomas (CRC). Age at CRC diagnosis was delayed by 15 years compared with classic FAP. Eighty-two patients had a colectomy and an ileorectal anastomosis and 5/82 (6%) had a secondary proctectomy. The location of the mutation in the APC gene was known in 69/171 (40%) tested patients. Only 15/29 (52%) of mutations in APC were found in parts of the gene usually associated with AFAP (the 5' end, exon 9 and 3' end). A subset of FAP patients with a milder phenotype does exist and treatment and surveillance had to be modified accordingly. The mutation detection rate is lower than in classic FAP and mutations in AFAP patients are located throughout the APC gene. We propose the following clinical diagnostic criteria for AFAP: a dominant mode of inheritance of colorectal adenomatosis and <100 colorectal adenomas at age 25 or older. Colonoscopy had to be preferred to sigmoidoscopy and surveillance had to be life-long. In the majority of patients, prophylactic colectomy and ileorectal anastomosis are recommended at the age of 20-25 years.
    Colorectal Disease 10/2010; 12(10 Online):e243-9. DOI:10.1111/j.1463-1318.2010.02218.x · 2.02 Impact Factor
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    ABSTRACT: Individuals with hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome) have a high risk for developing colorectal cancer (CRC). We evaluated the efficacy of annual surveillance colonoscopies to detect adenomas and CRCs. In a prospective, multicenter cohort study, 1126 individuals underwent 3474 colonoscopies. We considered individuals from 3 groups of HNPCC families: those with a pathogenic germline mutation in a mismatch repair gene (MUT group), those without a mutation but with microsatellite instability (MSI group), and those who fulfilled the Amsterdam criteria without microsatellite instability (MSS group). Compliance to annual intervals was good, with 81% of colonoscopies completed within 15 months. Ninety-nine CRC events were observed in 90 patients. Seventeen CRCs (17%) were detected through symptoms (8 before baseline colonoscopy, 8 at intervals >15 months to the preceding colonoscopy, and 1 interval cancer). Only 2 of 43 CRCs detected by follow-up colonoscopy were regionally advanced. Tumor stages were significantly lower among CRCs detected by follow-up colonoscopies compared with CRCs detected by symptoms (P = .01). Cumulative CRC risk at the age of 60 years was similar in the MUT and MSI groups (23.0% combined; 95% confidence interval [CI], 14.8%-31.2%) but considerably lower in the MSS group (1.8%; 95% CI, 0.0%-5.1%). Adenomas at baseline colonoscopy predicted an earlier occurrence of subsequent adenoma (hazard ratio, 2.6; 95% CI, 1.7-4.0) and CRC (hazard ratio, 3.9; 95% CI, 1.7-8.5), providing information about interindividual heterogeneity of adenomas and kinetics of CRC formation. Annual colonoscopic surveillance is recommended for individuals with HNPCC. Less intense surveillance might be appropriate for MSS families.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 10/2009; 8(2):174-82. DOI:10.1016/j.cgh.2009.10.003 · 6.53 Impact Factor
  • EJC Supplements 09/2009; 7(2):320-321. DOI:10.1016/S1359-6349(09)71095-X · 9.39 Impact Factor
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    ABSTRACT: Hereditary non-polyposis colorectal cancer, an autosomal dominant predisposition to colorectal cancer and other malignancies, is caused by inactivating mutations of DNA mismatch repair genes, mainly MLH1 and MSH2. Missense mutations affect protein structure or function, but may also cause aberrant splicing, if located within splice sites (ss) or cis-acting sequences of splicing regulatory proteins, i.e., exonic splicing enhancers or exonic splicing silencers. Despite significant progress of ss scoring algorithms, the prediction for the impact of mutations on splicing is still unsatisfactory. For this study, we assessed ten ss and nine missense mutations outside ss in MLH1 and MSH2, including eleven newly identified mutations, and experimentally analyzed their effect at the RNA level. We additionally tested and compared the reliability of several web-based programs for the prediction of splicing outcome for these mutations.
    Journal of Cancer Research and Clinical Oncology 09/2009; 136(1):123-34. DOI:10.1007/s00432-009-0643-z · 3.01 Impact Factor
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    ABSTRACT: Familial colorectal cancer (CRC) accounts for 10-15% of all CRCs. In about 5% of all cases, CRC is associated with a highly penetrant dominant inherited syndrome. The most common inherited form of non-polyposis CRC is the Lynch syndrome which is responsible for about 2-4% of all cases. Surveillance of individuals at high risk for CRC prevents the development of advanced CRC. About 1 million individuals in Western Europe are at risk for Lynch syndrome. We performed a survey to evaluate the strategies currently used to identify individuals at high risk for CRC in 14 Western European countries. Questionnaires were distributed amongst members of a European collaborative group of experts that aims to improve the prognosis of families with hereditary CRC. The survey showed that in all countries obtaining a family history followed by referral to clinical genetics centres of suspected cases was the main strategy to identify familial and hereditary CRC. In five out of seven countries with a (regional or national) CRC population screening program, attention was paid in the program to the detection of familial CRC. In only one country were special campaigns organized to increase the awareness of familial CRC among the general population. In almost all countries, the family history is assessed when a patient visits a general practitioner or hospital. However, the quality of family history taking was felt to be rather poor. Microsatellite instability testing (MSI) or immunohistochemical analysis (IHC) of CRC are usually recommended as tools to select high-risk patients for genetic testing and are performed in most countries in patients suspected of Lynch syndrome. In one country, IHC was recommended in all new cases of CRC. In most countries there are no specific programs on cancer genetics in the teaching curriculum for medical doctors. In conclusion, the outcome of this survey and the discussions within an European expert group may be used to improve the strategies to identify individuals at high risk of CRC. More attention should be given to increasing the awareness of the general population of hereditary CRC. Immunohistochemical analysis or MSI-analysis of all CRCs may be an effective tool for identifying all Lynch syndrome families. The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment.
    Familial Cancer 09/2009; 9(2):109-15. DOI:10.1007/s10689-009-9291-3 · 1.62 Impact Factor
  • Gabriela Möslein
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    ABSTRACT: Lynch syndrome (synonymous for HNPCC = hereditary non-polyposis colorectal cancer) is characterized by the development of colorectal, endometrial, gastric, and various other cancers, and is caused by a mutation in one of the mismatch repair (MMR) genes. One of the main challenges in the clinical management of Lynch syndrome remains the broad spectrum and heterogeneity among and between affected families. To date, no clinically relevant genotype-phenotype correlation for the two main affected genes hMSH2 and hMLH1 has been established. Clinical management of familial colorectal cancer (CRC) remains a challenge for clinicians. The overlap of syndromes with different underlying genetic causes and the differentiated risk management of colorectal and associated malignancies require state-of-the-art management recommendations.Regarding the identification of Lynch syndrome, the available criteria (revised Bethesda guidelines) appear to be effective for the selection of families for analysis of tumor MMR status. To date, the significant proportion of mutation carriers in Germany are still unknown and diagnosis still relies on patients with index cancers. Taking into account the tremendous importance the identification of MMR mutation carriers implies, future directives could include routine antibody staining for MMR genes in all CRCs. Increasing evidence suggests that microsatellite instability (MSI) and/or immunohistochemical (IHC) are an important prognostic factor and may predict the response to chemotherapy, therefore a broad application of these tools is envisaged in the near future.
    Hereditary Tumors: From Genes to Clinical Consequences, 08/2009: pages 281 - 294; , ISBN: 9783527627523
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    ABSTRACT: The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008.
    Human Mutation 05/2009; 30(4):496-510. DOI:10.1002/humu.20972 · 5.05 Impact Factor
  • Journal of Surgical Research 02/2009; 151(2):298-298. DOI:10.1016/j.jss.2008.11.659 · 2.12 Impact Factor
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    ABSTRACT: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon. In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome. Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed. The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)
    New England Journal of Medicine 01/2009; 359(24):2567-78. DOI:10.1056/NEJMoa0801297 · 54.42 Impact Factor
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    ABSTRACT: An ambitious plan to collect, curate, and make accessible information on genetic variations affecting human health is beginning to be realized.
    Science 12/2008; 322(5903):861-2. DOI:10.1126/science.1167363 · 31.48 Impact Factor
  • G. Möslein
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    ABSTRACT: Wesentliche Herausforderungen in der klinischen Betreuung von Patienten mit einer familiären Veranlagung zu kolorektalen Karzinomen bleiben weiterhin die Überschneidung der verschiedenen Entitäten mit unterschiedlicher genetischer Grundlage sowie das differenzierte Management der kolorektalen und deren assoziierten Malignome. Das Lynch-Syndrom (hereditäres nichtpolypöses kolorektales Karzinom, HNPCC) ist durch die Entstehung von kolorektalen-, Endometrium-, Magen- und anderen Karzinomen charakterisiert und wird durch eine Mutation in einem der Mismatch-Reparaturgene (MMR) verursacht. Die Mikrosatelliteninstabilität (MSI) und/oder immunhistochemische Befunde (IHC) sind wichtige Faktoren und haben prognostische Bedeutung für das Ansprechen auf eine Chemotherapie. Die familiäre adenomatöse Polyposis (FAP) ist für <1% aller kolorektalen Karzinome verantwortlich und mag als polypenreiches Pendant zum Lynch-Syndrom gesehen werden. Kürzlich wurde das MUTYH als weiteres Polyposisgen identifiziert. Die begleitende Krankheitsausprägung wird als MYH-assoziierte Polyposis (MAP) bezeichnet und weist ein autosomal-rezessives Vererbungsmuster auf. Für den Kliniker ist die Unterscheidung zwischen dem Lynch-Syndrom, der attenuierten FAP und der MAP zur Risikoeinschätzung, Vorsorgeempfehlung und Indikation zu einer prophylaktischen Chirurgie essenziell. One of the main challenges in the clinical management of familial colorectal cancer (CRC) remains the overlap of syndromes with different underlying genetic causes and the differentiated risk management of colorectal and associated malignancies. The Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is characterized by the development of colorectal, endometrial, gastric and other cancers and is caused by a mutation in one of the mismatch repair (MMR) genes. Microsatellite instability (MSI) and/or immunohistochemistry (IHC) are important prognostic factors and may predict the response to chemotherapy. Familial adenomatous polyposis (FAP) may be seen as a counterpart to Lynch syndrome, responsible for <1% of all CRC cases. Recently the MUTYH gene has been identified as a further polyposis gene. The associated disorder has been termed MYH-associated polyposis (MAP) and displays an autosomal recessive pattern of inheritance. For clinical management, distinguishing between Lynch syndrome, attenuated FAP and MAP is important for risk assessment, surveillance recommendations and indication for prophylactic surgery.
    Der Chirurg 11/2008; 79(11):1038-1046. DOI:10.1007/s00104-008-1557-z · 0.52 Impact Factor
  • G Möslein
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    ABSTRACT: One of the main challenges in the clinical management of familial colorectal cancer (CRC) remains the overlap of syndromes with different underlying genetic causes and the differentiated risk management of colorectal and associated malignancies. The Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is characterized by the development of colorectal, endometrial, gastric and other cancers and is caused by a mutation in one of the mismatch repair (MMR) genes. Microsatellite instability (MSI) and/or immunohistochemistry (IHC) are important prognostic factors and may predict the response to chemotherapy. Familial adenomatous polyposis (FAP) may be seen as a counterpart to Lynch syndrome, responsible for <1% of all CRC cases. Recently the MUTYH gene has been identified as a further polyposis gene. The associated disorder has been termed MYH-associated polyposis (MAP) and displays an autosomal recessive pattern of inheritance. For clinical management, distinguishing between Lynch syndrome, attenuated FAP and MAP is important for risk assessment, surveillance recommendations and indication for prophylactic surgery.
    Der Chirurg 10/2008; 79(11):1038-46. · 0.52 Impact Factor
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    ABSTRACT: Ten non-synonymous single nucleotide polymorphisms (nsSNPs), which were recently associated with colorectal cancer risk in a comprehensive, array based study (AKAP9 M463I, DKK3 G335R, AMPD1 Q12X, LIPC L356F, PSMB9 V32I, THBS1 N700S, CA6 S90G, ASCC3 C1995S, DHX36 S416C and CPA4 G303C) were re-evaluated in the present study based on 626 German familial non-HNPCC colorectal cancer patients and 736 healthy controls. No associations of any of the 10 nsSNPs with colorectal cancer could be replicated. The combined analyses indicated that further research based on additional independent samples is required.
    Cancer letters 08/2008; 271(1):153-7. DOI:10.1016/j.canlet.2008.05.043 · 5.02 Impact Factor
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    ABSTRACT: To determine the prevalence of adenomatous and hyperplastic polyps in a large cohort of individuals with a germline mutation in a mismatch repair (MMR) gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer (HNPCC). These prevalences have been estimated previously in smaller studies, and the results have been found to be variable. Colorectal Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in people classified as having HNPCC. The 695 patients with a proven germline MMR mutation and documented screening history before the chemoprevention study were the focus of this study. The number, histology, size, and location of polyps found at the participants' first ever colonoscopy were analyzed in a cross-sectional study. Seventy-four patients (10.6%) were found to have at least one adenoma at first colonoscopy, whereas 37 (5.3%) had at least one hyperplastic polyp. The frequency of an adenoma at first colonoscopy increased from 5.0% (95% CI, 2.8% to 8.3%) in patients younger than 35 years old to 18.9% (95% CI, 9.4% to 32.0%) in patients age at least 55 years (P = .0001 for trend). No such trend was observed for hyperplastic polyps. No sex differences were found for either type of polyp. A marginal association was found between the co-occurrence of adenomas and hyperplastic polyps. Adenomas tended to be more proximally distributed through the colon, whereas hyperplastic polyps tended to be located in the distal colon. Adenoma prevalence increases with age among MMR mutation carriers, whereas hyperplastic polyp prevalence is consistent. No sex differences were observed for either type of lesion.
    Journal of Clinical Oncology 08/2008; 26(20):3434-9. DOI:10.1200/JCO.2007.13.2795 · 17.88 Impact Factor
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    ABSTRACT: Expression profiling is a well established tool for the genome-wide analysis of human cancers. However, the high sensitivity of this approach combined with the well known cellular and molecular heterogeneity of cancer often result in extremely complex expression signatures that are difficult to interpret functionally. The majority of sporadic colorectal cancers are triggered by mutations in the adenomatous polyposis coli (APC) tumor suppressor gene, leading to the constitutive activation of the Wnt/beta-catenin signaling pathway and formation of adenomas. Despite this common genetic basis, colorectal cancers are very heterogeneous in their degree of differentiation, growth rate, and malignancy potential. Here, we applied a cross-species comparison of expression profiles of intestinal polyps derived from hereditary colorectal cancer patients carrying APC germline mutations and from mice carrying a targeted inactivating mutation in the mouse homologue Apc. This comparative approach resulted in the establishment of a conserved signature of 166 genes that were differentially expressed between adenomas and normal intestinal mucosa in both species. Functional analyses of the conserved genes revealed a general increase in cell proliferation and the activation of the Wnt/beta-catenin signaling pathway. Moreover, the conserved signature was able to resolve expression profiles from hereditary polyposis patients carrying APC germline mutations from those with bi-allelic inactivation of the MYH gene, supporting the usefulness of such comparisons to discriminate among patients with distinct genetic defects.
    American Journal Of Pathology 06/2008; 172(5):1363-80. DOI:10.2353/ajpath.2008.070851 · 4.60 Impact Factor

Publication Stats

4k Citations
687.86 Total Impact Points

Institutions

  • 2006–2014
    • HELIOS St. Josefs-Hospital Bochum-Linden
      Bochum, North Rhine-Westphalia, Germany
    • Leiden University
      • Molecular Cell Biology Group
      Leyden, South Holland, Netherlands
    • Technische Universität Dresden
      • Department of Visceral, Thoracic and Vascular Surgery
      Dresden, Saxony, Germany
  • 2008–2013
    • Leiden University Medical Centre
      • Department of Gastroenterology and Hepatology
      Leyden, South Holland, Netherlands
  • 2012
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 2000–2007
    • Heinrich-Heine-Universität Düsseldorf
      • • Institute of Neuropathology
      • • Department of Trauma and Hand Surgery
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2004–2006
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2001–2004
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1995
    • Universität Heidelberg
      • Surgical Hospital
      Heidelberg, Baden-Wuerttemberg, Germany