Benutzerspezifische Werkzeuge

Molecular Etiology of Colorectal Cancer

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Familial adenomatous
polyposis coli (FAP)
(autosomal dominant)
Gene: APC

MUTYH-associated
polyposis

(autosomal recessive)
Gene: MUTYH

Hereditary Nonpolyposis
Colorectal Cancer Syndrome
(HNPCC, Lynch Syndrome)
(autosomal dominant)
Mismatchrepair Genes:
MSH2, MLH1, MSH6, PMS2 

Sporadic CRC








To identify HNPCC patients revised Bethesda Guidelines have been established
(Umar et al., 2004)

Summary of revised Bethesda Guidelines:

Family history
and/or
Several tumors in one patient
and/or
Early age of disease onset
and
No polyposis

If patients meet revised Bethesda Guidelines
tumor diagnostics is recommended


 Loss of protein expression in the tumor identifies the mutated MMR gene

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Sequencing of the respective gene in lekocyte DNA identifies the germline mutation

DNA

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Predictive testing can be offered to family members
(after genetical counselling)

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Recommendation of HNPCC-specific surveillance program

  


191 mutations identified at the Dresden Center
German HNPCC Consortium
Centers in Bonn, Bochum, Dresden, Düsseldorf, Heidelberg, Munich

144  pathogenic mutations

MLH1

64

795  pathogenic mutations

MSH2

MSH6

PMS2

53

19

8

47    unclassified variants

MLH1

19

235  unclassified variants

MSH2

MSH6

PMS2 

12

8

8


Predictive diagnostics at the Dresden Center

Diagramm


  

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