HNPCC, molecular and clinical dilemmas
Wagner, A.
Citation
Wagner, A. (2005, April 27). HNPCC, molecular and clinical dilemmas. Macula, Boskoop.
Retrieved from https://hdl.handle.net/1887/2719
Version:
Corrected Publisher’s Version
License:
Licence agreement concerning inclusion of doctoral thesis in the
Institutional Repository of the University of Leiden
Downloaded from:
https://hdl.handle.net/1887/2719
List of tables and figures
T ables.
Table 1.
Proven and “candidate” H N PC C genes.
14
Table 2.
The Amsterdam criteria for the clinical diagnosis of H N PC C Families. 14
Table 3.
The Bethesda guidelines to select for MSI testing
of colorectal tumours.
16
Table 4.
Selected markers for MSIanalysis in colorectal cancer
and criteria for the interpretation of MSI.
16
Table 5.
C umulative lifetime risks of colorectal, endomterial, stomach,
ovarian, urothelial, small bowel, biliary tract cancer and brain
tumours in MLH1, MSH2 and MSH6 mutation carriers compared
to the population risks.
33
Table 6.
Mean age of onset of colorectal, endometrial, stomach, ovarian,
urothelial, small bowel, biliary tract cancer and brain tumours
in MLH1, MSH2 and MSH6 mutation carriers.
33
Table 7.
Screening advises in H N PCC (-like) families.
38
Table 8.
C omparison of MSI and IH C analysis in 154 tumours of 119 families
analysed for MLH1, MSH2 and sometimes MSH6 mutations.
51
Table 9.
Logistic regression model for selection for MSH2, MLH1 mutation
analysis.
51
Figures.
Figure 1.
A.S. W arthin (1866-1931), H .T. Lynch.
13
Figure 2.
The crystal structure of the MutS dimer.
17
Figure 3.
Schematic representation of the eukaryotic mismatch repair
(MMR) pathways.
22
Figure 4.
Schematic representation of the Knudson model.
24
Figure 5.
The adenoma-carcinoma sequence.
26
Figure 6.
A schematic representation of the W nt-signalling pathway.
27
Figure 7.
A schematic representation of the KRAS-signalling pathway.
28
Figure 8.
A schematic representation of the TGFE-signalling pathway.
29
Figure 9.
A schematic representation of the p53-pathway.
30
Figure 10.
A practical flowchart for the management of individuals with
multiple or early onset H N PC C -associated tumours, and of
families with clustering of H N PC C -associated tumours.
50
Curriculum Vitae
Anja Wagner werd op 13 december 1968 te Rotterdam geboren.
1973-1975
Kleuterschool “O ud Charlois” te Rotterdam.
1975-1981
D erde Rotterdamse Schoolvereniging.
1981-1987
Gymnasium Erasmianum te Rotterdam.
1987-1995
Studie Geneeskunde, Erasmus U niversiteit Rotterdam.
1992/3
Afstudeeronderzoek “D e behandeling en prognose van onstabiele
angina pectoris op de ICCU van een Indonesisch ziekenhuis”,
U jung Pandang, Sulawesi.
1995-1999
AGNIO afdeling Klinische Genetica, Erasmus Medisch Centrum
Rotterdam, in het bijzonder bij genetisch onderzoek en advies bij
erfelijke tumoren onder leiding van Prof. D r. M.F. Niermeijer en
D r. E.J. Meijers-Heijboer.
1999-2004
AGIKO afdeling Klinische Genetica, Erasmus Medisch Centrum Rotterdam;
opleiding onder leiding van Prof. D r. M.F. Niermeijer en D r. E.J.
Meijers-Heijboer, promotie onderzoek onder leiding van Prof. D r. R. Fodde,
afdeling Humane en Klinische Genetica, Leids U niversitair Medisch
Centrum.
2004-heden
Klinisch Geneticus afdeling Klinische Genetica, Erasmus Medisch
Centrum Rotterdam, verantwoordelijk voor de patiëntenzorg op de
Polikliniek Erfelijke Maag-, D arm-, Leverziekten, de polikliniek Erfelijke
Kinderoncologie en contactpersoon met betrekking tot genodermatosen.
Tijdens haar studie geneeskunde was Anja één van de oprichters van de “Werkgroep
Andere Geneeswijzen”, welke tot doel had studenten over andere geneeswijzen dan de
reguliere te informeren. In 2000 was zij enkele weken te gast bij Prof. D r. H.T. Lynch op
de afdeling Public Health and Preventive Medicine, Creighton U niversity, O maha, U SA. Zij
woonde daar enkele informatieve familie-bijeenkomsten bij. Tenslotte was zij als
deskundige betrokken bij het opzetten van de “Werkgroep Erfelijkheid” van de
Borstkanker Vereniging Nederland (BVN).
List of publications
Wagner A, et al. Preliminary experience with predictive testing for insulin-dependent diabetes mellitus. Lancet 1995:346;380-381
Verhoog LC, Brekelmans C, Seynaeve C, Bosch L van den, Dahmen G, Geel AN van, Tilanus M, Bartels C, Wagner A, et al. Survival and tumour caracteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 1998:35;316-21
Verhoog LC, Brekelmans C, Seynaeve C, Dahmen G, Geel AN van, Bartels CC, Tilanus-Linthorst MM, Wagner A, et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2. JClinOncol 1999:17;3396-3402
Lodder LN, Frets PG, Trijsburg RW, Meijers-Heijboer EJ, Klijn JGM, Duivenvoorden HJ, Tibben A, Wagner A et al. Presymptomatic testing for BRCA1 and BRCA2: how distressing are the pretest weeks? JMedGenet 1999:36;906-13
Meijers-Heijboer EJ, Verhoog LC, Brekelemans CTM, Seynaeve C, Tilanus-Linthorst MMA, Wagner A et al. Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation. Lancet 2000 :355;2015
Wagner A, et al. Atypical HNPCC owing to MSH6 germline mutations; study of a large Dutch pedigree. J Med Genet 2001;38:318-22
Stella A, Wagner A, et al. A nonsense mutation in MLH1 causes exon skipping in three unrelated HNPCC families. Cancer Research 2001;61:7020-4
Verhoog LC, van den Ouweland AMW, Berns E, van Veghel-Plandsoen MM, van Staveren IL, Wagner A, et al. Large regional differences in frequency of distinct BRCA1/BRCA2 mutations in 157 Dutch breast and/or ovarian cancer families. EurJCancer 2001:37;2082-2090
Lodder LN, Frets PG, Trijsburg RW, Meijers-Heijboer EJ, Klijn JGM, Duivenvoorden HJ, Tibben A, Wagner A, et al. Psychological impact of receiving a BRCA1/BRCA2 test result. AmJMed Genet 2001:98 ;15-24
Lodder LN, Frets PG, Trijsburg RW, Tibben A, Meijers-Heijboer EJ, Duivenvoorden HJ, Wager A, et al. Men at risk of being a mutation carrier for hereditary breast/ovarian cancer: an exploration of attitudes and psychologicalfunctioning during genetic testing. EurJHumGenet 2001:9 ;492-500 Wagner A, et al. A 10Mb paracentric inversion of chromosome 2p inactivates MSH2 and is responsible for
HNPCC in a North-American kindred. Genes, Chromosomes and Cancer 2002;35:49-57 Wagner A, et al. Genetic testing in Hereditary nonpolyposis colorectal cancer families with a MSH2,
MLH1 or MSH6 mutation. JMG 2002;39:833-7
Wagner A, et al. Molecular Analysis of Hereditary Nonpolyposis Colorectal Cancer in the United States: High Mutation Detection Rate among Clinically Selected Families and Characterization of an American Founder Genomic Deletion of the MSH2 gene. Am J Hum Genet 2003;72:1088-1100 Meijers-Heijboer H, Wijnen J, Vasen H, Wasielewski M, Wagner A, et al. The check2 1100delC mutation
identifies families with a hereditary breast and colorectal cancer phenotype. Am Jhum Genet 2003:72;1308-1314
Lynch HT, Taylor RJ, Lynch J, Knezetic JA, Barrows A, Fodde R, Wijnen J, Wagner A, et al. Multiple primary cancer, including transitional cell carcinoma of the upper uroepithelial tract in a multigeneration HNPCC family: Molecular and management implications. AmJGastroent 2003:98;664-670
Watson P, Narod SA, Fodde R, Wagner A, et al. Carrier risk status changes resulting from mutation testing in hereditary non-polyposis colorectal cancer and hereditary breast-ovarian cancer. Jmed Genet 2003:40;591-596
Lynch HT, Coronel S, Okimoto R, Hampel H, Sweet K, Lynch JF, Barrows A, Wijnen J, Klift H van der, Franken P, Wagner A, et al. A Founder Mutation of the MSH2 gene and Hereditary Nonpolyposis Colorectal Cancer in the United States.JAMA 2004;291:718-24
Hendriks YMC, Wagner A, et al. Cancer Risk in Hereditary Non Polyposis Colorectal Cancer Associated with MSH6 Mutations; Consequences for Counselling and Surveillance. Gastroenterology 2004:27;17-25
Jong AE de, Puijenbroek M van, Hendriks Y, Tops C, Wijnen J, Ausems M, Meijers-Heiboer EJ, Wagner A et al. Microsatellite Instability, Immunohistochemistry,and Additional PMS2 staining in Suspected Hereditary Nonpolyposis Colorectal Cancer. Clin Cancer Res 2004;10:972-80 Seynaeve C, Verhoog LC, van de Bosch LMC, van Geel AN, Menke-Pluijmers M, Meijers-Heijboer EJ, van
en OuwelaND amw, Wagner A, et al. Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy. EurJCancer 2004:40;1150-1158
Klevering BJ, Maugeri A, Wagenr A, et al. Three families displaying the combination of Stargardt’s disease with cone-rod dystrophy or retinitis pigmentosa. Ophthalmology 2004:111;546-553
