Chapter 1 Flashcards
The coding sequence, which dictates protein sequences, is contained within
Exons
Mutations in genes encoding components of the telomere complex are associated with the bone marrow failure syndrome
Dyskeratosis congenita
The spliceosome is a large complex of proteins and five
Small nuclear ribonuclear proteins (snRNPs)
What are the 3 splicing factor mutations found in approximately 50% of patients with MDS?
SF3B1, U2AF1, SRSF2
DNA sequences that lie in proximity to and regulate the expression of genes, which encode protein, are termed
Cis-acting regulatory elements
A special type of enhancer is locus control region (LCR), which is located approximately 50 kilobases upstream from this gene.
Beta-globin
In addition to being complexed with protein, the DNA of inactive genes is modified by the addition of methyl groups to
Cytosine residues
The addition of methyl groups to cytosine residues of inactive genes results in
5-methylcytosine (5mC)
Is methylation generally a marker of an active or inactive gene?
Inactive
DNA methylation is performed by enzymes called
DNA methyltransferases
When genes are ______, they are usually heavily methylated in contrast to the nonimprinted copy of the allele.
Imprinted
When genes are imprinted, they are usually heavily ______ in contrast to the nonimprinted copy of the allele.
Methylated
Hematopoietic stem cells display an age-related decline in function and a relative loss of lymphoid differentiation potential, and these changes are associated with site-specific changes in
DNA methylation
Hematopoietic stem cells display an age-related decline in function and a relative loss of ______ differentiation potential, and these changes are associated with site-specific changes in DNA methylation.
Lymphoid differentiation
Mutations in enzymes affecting DNA methylation, most notably the DNA methyltransferase ______ are common in AML.
DNMT3A
Mutations in DNMT3A are found in approximately ______ of AML patients.
20%
What are the 3 major enzymes affecting DNA methylation that are recurrently mutated in AML?
DNMT3A, TET2, IDH1/2
Small molecule inhibitors of DNA methyltransferases are used in the treatment of disorders that are characterized by aberrant DNA methylation such as
MDS, AML
What are the 2 major small molecule inhibitors of DNA methyltransferases?
5-azacitidine, decitabine
Histones are DNA packaging proteins that organize DNA into structural units called
Nucleosomes
Hypoacetylation of these 2 histones is associated with silencing of the cell cycle regular p21, a gene whose expression is reduced in multiple tumor types.
H3, H4
Hypoacetylation of histones H3 and H4 is associated with silencing of the cell cyle regulator
p21
These are the enzymes that remove acetyl groups from histone tails.
Histone deacetylases (HDACs)
Aberrant expression levels of histone deacetylases (HDACs) are common in ______ malignancies.
Hematologic
This is the first HDAC inhibitor.
Vorinostat AKA SAHA (Zolinza)
Oncogenes arise from mutations in their normal counterparts termed
Proto-oncogenes
Translocation between the BCR gene on chromosome 9 and the ABL1 proto-oncogene on chromosome 22 concerns constitutive
Activation of ABL1
Li-Fraumeni syndrome results from inherited mutations in the cell cycle regulator
TP53
In the case of some tumor suppressor genes, loss of just one copy of a gene is known as
Haploinsufficiency
Haploinsufficiency of the ribosomal gene RPS14 in this syndrome leads to aberrant ribosomal protein function and a block in erythroid differentiation.
5q- syndrome
Haploinsufficiency of the ribosomal gene ______ in 5q- syndrome leads to aberrant ribosomal protein function and a block in erythroid differentiation.
RPS14
Haploinsufficiency of the ribosomal gene RPS14 in 5q- syndrome leads to aberrant ribosomal protein function and a block in
Erythroid differentiation
DNA can be visualized using gel electrophoresis by staining with
Ethidium bromide
This technique is a modification of PCR that allows the detection and amplification of expressed RNA transcripts.
Reverse transcriptase PCR (RT-PCR)
This is the most commonly used method for quantitative PCR.
Real-time PCR
This PCR technique is used to measure minimal residual disease and to monitor the clearance of BCR/ABL transcriptions in patients treated with tyrosine kinase inhibitors.
Real-time PCR
The technique of molecular hybridization is the basis for ______ blotting.
Southern
This technique is analogous to Southern blotting, but it involves electrophoresis of RNA with subsequent transfer and hybridization to a probe.
Northern blotting
______ blotting detects the presence of a gene or its integrity.
Southern
______ blotting detects the level of expression of a gene within a specific cell type.
Northern
______ blotting detects proteins.
Western
t(15;17) is considered pathognomonic of
Acute promyelocytic leukemia (APL)
The major advantage of FISH is that it can analyze known cytogenetic abnormalities in ______ cells.
Nondividing cells (interphase nuclei)
MYC translocations are associated with
Burkitt lymphoma
CCND1 translocations are associated with
Mantle cell lymphoma
