Molecular Basis of Carcinogenesis II Flashcards
FAP is inherited in an _______ fashion, in which patients that inherit one defective _______ gene will be at _______ risk to develop colon cancer
autosomal dominant
APC
higher (90% will develop colon cancer by age 50)
colon
Cancer develops when the wild-type gene is lost by _______ in cells in _______ during the first 20 years. Thus, these benign _______ may become malignant
LOH
adenomatous polyps of the colon
adenomatous polyps
APC gene was isolated by _______ after it was mapped to chromosome _______ by genetic linkage and _______. The molecular information can be used clinically to identify _______
positional cloning
5q
LOH studies
high-risk patients for therapy
APC gene encodes
a cytoplasmic protein that regulates the localization of the Beta-catenin protein
Beta-catenin is kept at the _______ by: _______
- plasma membrane
- being bound to E-cadherin in normal cells
The APC protein causes _______. When the APC is lost in FAP patients, _______. Thus, loss of APC tumor suppressor causes _______
- the degradation of any unbound and free Beta-catenin in the cytoplasm
- Beta-catenin goes to the nucleus to produce transcription of oncogenes like c-myc
- an overexpression of the c-myc oncogene, resulting in cancer!
In Breast and ovarian cancers, there are two similar predisposing genes:
BRCA1 and BRCA2
About 5% of woman with breast cancers have inherited mutations in the BRCA1 or 2 _______ genes. These cases therefore display _______ and have _______ genes.
- inherited mutations in the BRCA1 or 2
- LOH
- only mutant BRCA1 or 2
the acquired cases, it is believed that _______ may affect BRCA1 and BRCA2 function _______.
- mutations in other genes
- indirectly
Both BRCA1 and BRCA2 function in _______
DNA repair
BRCA2 has been shown to be allelic with
the Fanconi’s anemia D1 gene, FANCD1
individuals with homozygous mutations in BRCA2 get _______, while heterozygotes get _______
- Fanconi’s anemia
- breast cancer from rare recombinant cells in the mammary gland that lose the wild-type allele.
p53 is a _______. It also is important for the response of cells to _______.
- tumor suppressor gene
- environmental mutagenesis
Cells missing p53
accumulate mutations at a much higher rate and thereby, have a greater chance of becoming malignant.
oncogenic p53 mutations produce
a mutant p53 protein that can bind the wild-type p53 protein and inactivate it. These “dominant-negative” p53 mutations can be viewed as “spoilers” or “monkey wrenches”
