dr Naidoo Flashcards
What are the main factors contributing to the development of cancer?
Cancer development is influenced by environmental factors (such as smoking and lifestyle choices) and genetic factors (mutations in specific genes), or a combination of both.
What are the different classes of genes involved in cancer development?
Different classes of genes include tumor suppressor genes (e.g., p53, APC), oncogenes (e.g., Bcl2, RAS), DNA repair genes (e.g., hMLH1, hMSH2), and cell cycle genes (e.g., p16, Cyclins).
How do microsatellites contribute to cancer development?
Microsatellites are short tandem repeat sequences in DNA. Their instability, known as microsatellite instability (MSI), can lead to genetic alterations that contribute to the development of both inherited and sporadic cancers.
Describe the process of microsatellite instability (MSI).
MSI is caused by DNA slippage during replication, where repeat sequences in microsatellites experience mispairing. This leads to changes in the number of repeat motifs, resulting in instability.
What is the significance of DNA repair genes in cancer prevention?
DNA repair genes play a crucial role in maintaining genome integrity by correcting DNA damage caused by various factors, such as UV radiation, chemicals, and replication errors. They act as guardians of the genome, preventing the accumulation of mutations that can lead to cancer.
How is microsatellite instability (MSI) assessed in tumors?
MSI is assessed using microsatellite markers. Tumor tissues are compared to normal tissues to detect variations in microsatellite repeat lengths. The status is categorized as MSS (microsatellite stable), MSI-High (multiple markers with instability), or MSI-Low (instability in a smaller number of markers).
What are the Jerusalem Criteria in the context of colorectal cancer testing?
The Jerusalem Criteria recommend genetic testing for colorectal cancer patients under 70 years old, using immunohistochemistry for DNA mismatch repair gene products. Additional analyses, such as BRAF mutation or methylation of MLH1 promoter, are suggested for specific cases.
Explain the two-hit theory of carcinogenesis.
The two-hit theory, proposed by Knudson, states that for tumor formation, two mutant alleles are required. Inherited mutation of one allele must be followed by an acquired second mutation to lead to tumor development.
What is the significance of microsatellite instability (MSI) in hereditary non-polyposis colorectal cancer (HNPCC)?
MSI is observed in HNPCC due to germline mutations in DNA mismatch repair genes. It leads to MSI-High tumors that arise in the proximal colon, have distinct features, and better prognosis compared to MSI-Low or MSS tumors.
How do immunohistochemistry assays help in identifying DNA mismatch repair deficiencies?
Immunohistochemistry assays detect the loss of MMR gene proteins. This loss indicates either a gene mutation or promoter hypermethylation. The assays can predict MSI status and differentiate between MSI-High and MSS tumors.
What is the role of the serrated pathway in colorectal cancer development?
The serrated pathway is a recently described subset of CRC development. It involves the transformation of serrated polyps into CRC, with KRAS and BRAF mutations contributing. MSI and CpG island methylator phenotype play roles in this pathway.
How do the Jerusalem Criteria impact the clinical management of colorectal cancer?
The Jerusalem Criteria recommend genetic testing for colorectal cancer patients, including immunohistochemistry analysis for DNA mismatch repair gene products. Additional tests like BRAF mutation and MLH1 promoter methylation analysis are advised in specific cases
Describe the differences between microsatellite instability-high (MSI-H) and microsatellite instability-low (MSI-L) tumors.
MSI-H tumors have multiple markers with instability and are commonly associated with Lynch syndrome. In contrast, MSI-L tumors show instability in a smaller number of markers and have a phenotype similar to microsatellite stable (MSS) tumors.
How does microsatellite instability (MSI) impact the prognosis of colorectal cancer patients?
MSI-High tumors often exhibit better survival rates compared to MSS tumors. However, the prognostic significance of MSI-H in sporadic CRC remains uncertain due to variations in microsatellite markers and tumor characteristics.
What is the significance of the two-hit theory of carcinogenesis proposed by Knudson?
The two-hit theory explains that tumor formation requires mutations in both alleles of a specific gene. While one inherited mutant allele provides susceptibility, the acquisition of a second mutation is necessary for tumor development.
