LWBK1006-01 LWW-Govindan-Review November 24, 2011 11:17
Chapter 1•Molecular Biology of Cancer Part 1 11Answer 1.15. The answer is B.
SAHA and depsipetide are examples of histone deacetylase inhibitors
whereas 5-azacytidine and 5-Aza-2′-deoxycytidine are DNA hypomethy-
lating agents.Answer 1.16. The answer is D.
Mutations of p53 are among the most commonly identified in human
cancers. Wild-type p53 has a function in signaling cells with damaged
DNA to undergo programmed cell death (apoptosis). In the presence of
an inactivating mutation of p53, commonly used genotoxic agents, such as
radiation and chemotherapy, may prove less effective with the intact p53
signal. This has been demonstrated in preclinical models and correlates
with some human clinical trial data. It must be noted, however, that many
common malignancies harboring p53 mutations, such as small cell lung
cancer and ovarian cancer, are sensitive to chemotherapy and radiation.
The capacity of p53 to trigger apoptosis is associated with the cell-cycle
checkpoints that have been identified as critical nodal moments at which
the cell may “choose” to continue to divide or, if sufficiently damaged,
progress down a path to cell death and deletion of the potentially damaged
clone. Interestingly, p53 mutant transgenic mice are viable and develop
normally. However, they have an accelerated rate of tumor formation
under certain tumorigenic stimuli.Answer 1.17. The answer is D.
Gene amplification as a mechanism resulting in overexpression of gene
products involved in tumorigenesis or tumor progression has been
reported in several cancers. It is known that N-myc amplification in neu-
roblastoma can be a useful prognostic factor aiding in designing therapy.
In small cell lung cancer, c-myc amplification has been identified in up
to 10% of specimens, a percentage that may increase after treatment.
Her2/neu amplification occurs in up to 30% of breast cancers and is use-
ful in predicting response to Her2/neu-targeted therapy.Answer 1.18. The answer is B.
Microsatellite instability refers to frequent mutations in regions of sim-
ple repeat sequences. Early studies in kindreds with HNPCC demon-
strated mutations in MSH2 and MLH1, which are mismatch repair genes.
Approximately 85% of patients with HNPCC have mutations in MSH2
and MLH1. Microsatellite instability is associated with a resistance to
5-fluorouracil treatment, more favorable prognosis, and lack of p53 muta-
tions. The protein MSH2 complexes with MSH6 to recognize mismatched
bases, and subsequent recruitment of MLH1 and PMS2 initiates the steps
of repair (excision, DNA synthesis, and ligation).Answer 1.19. The answer is D.
The mismatch repair machinery of the cell includes two major pathways:
nucleotide excision repair (NER) and base excision repair (BER). These