FINALS: MOLECULAR ONCOLOGY Flashcards
study of tumors/neoplasm (growth of tissue that exceeds and is not coordinated with normal tissue).
Oncology
not recurrent; suffix -oma to the tissue of origin
Benign
invasive and tending to recur at multiple sites (cancer)
Malignant
movement of tumor cells from the original (primary) site of the
tumor to other locations
Metastasis
study of cancer at the molecular level
Molecular Oncology
a term that includes
all malignant tumors.
CANCER
CANCER:
an ABNORMAL MASS OF TISSUE that usually does not contain cysts or liquid areas
Solid tumors
SOLID TUMORS CANCER:
tumor of EPITHELIAL TISSUE origin
Carcinoma
SOLID TUMORS CANCER:
tumor of BONE, CARTILAGE, muscle, blood vessel, or fat
Sarcoma
SOLID TUMORS CANCER:
- consists of multiple cell types
- Common among them is that they are capable of formation of ___________
Teratocarcinoma
- angiogenesis
CANCER:
ABNORMAL CELLS in the blood grow out of control
Hematological malignancies
Hematological malignancies CANCER:
- neoplastic disease of blood-forming tissue in which large number of WBCs populate the bone marrow and peripheral blood
Leukemia
Hematological malignancies CANCER:
- neoplasm of lymphocytes that forms discrete tissue masses
i. Usually accumulates in the lymph nodes
ii. Purkitt’s lymphoma
Lymphoma
- arise from terminally differentiated B cells
- abnormal plasma cells or cells from tumors in the bones/soft tissues of the body
Plasma cell neoplasms
Cancer is caused by ________ mutations in DNA affecting 2 types of genes that control the cell division cycle and cell survival: ONCOGENES AND TUMOR SUPPRESSOR GENES
nonlethal mutations
- Promote cell division
- Include cell membrane receptors that are
bound by growth factors, hormones, and
other extracellular signals - Support cell survival by inhibiting apoptosis
- > 100 in the human genome
- Gain-of-function mutations resulting from
○ Amplification /translocation of DNA regions containing genes
○ Activating mutations that cause aberrant activity of the proteins
ONCOGENES
- Factors that control transcription/translation of genes required for cell division
- Participate in repairing DNA damage and in
promoting apoptosis - Slow down/stop cell division by counteracting the movement of the cell from G1-to S (G1
checkpoint) or G2 to M phase (G2 checkpoint) - > 30 in the human genome
- Loss-of-function mutations
○ Inactivation of the gene products (deletion, translocation, mutation of the genes)
~ Ex. p53
Tumor-suppressor genes
ANALYTICAL TARGETS OF MOLECULAR TESTING
- Molecular characteristics of the tissue from which a tumor arose
- Detection and monitoring the presence of
tumor
○ Abnormal amounts or locations of DNA, RNA, proteins and other
molecules from these targets
○ Examples: DNA & RNA from
a. CYTOKERATIN genes from gastric cancer
b. CARCINOEMBRYONIC ANTIGEN in breast cancer
Tissue-Specific Targets
ANALYTICAL TARGETS OF MOLECULAR TESTING
- Genetic structures resulting from mutations in oncogenes and tumor-suppressor genes that are associated with tumor development
- Solid tumors, leukemias, lymphomas
- Mutated cell-free nucleic acid/circulating
tumor cells can be detected in blood and
other body fluids
Tumor-Specific Targets
group of tumors arising from primitive neuroectodermal tissue
Diagnosis and prognosis:
1. cytogenetic methods
2. molecular methods:
RT-PCR, with amplification control
(GAPDH or 185 RNA)
on tissue/liquid biopsies
Ewing Sarcoma, EWS
(22q12)
rare type of cancer of the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body
Detection methods:
1. FISH
2. RT-PCR
3. Semi-nested PCR
4. Agarose gel
electrophoresis & EtBr
staining (PCR product
detection)
SYNOVIAL SARCOMA
translocation, chrmosome 18 -Synopvial sarcoma, breakpoint 1 & 2, SYT-
SSX1, SYT-SSX2 t(X;18)
(p11.2;q11.2)
most common soft tissue sarcoma of childhood (10% of all solid tumors in children)
➢ Alveolar RMS,
embryonal (RMS-E),
& primitive (RMS-P)all solid tumors in children)
➢ Alveolar RMS,
embryonal (RMS-E),
& primitive (RMS-P)
Detection methods: FISH, RT-PCR, qPCR, RNA
sequencing
Rhabdomyosarcoma (RMS)
● Contraction & expansion of nucleotide repeat sequences in DNA
● Cause: dysfunction of 1 or more components of mismatch repair (MMR) systems
MICROSATELLITE INSTABILITY (MSI)
recommended the screening of BAT25 & BAT26: & D5S346,
D25123, & D175250 for MSI determination
National Cancer Institute
● Deletion/inactivation of a functional allele, leaving a mutated allele
● Detection methods:
○ PCR & capillary electrophoresis: amplification of heterozygous STR/VNTR loci
closely linked to the disease gene
LOSS OF HETEROZYGOSITY
● A laboratory test done on a sample of blood (plasma/serum), urine, or other body fluid to
look for cells & nucleic acids released by the tumors into a person’s body fluids
LIQIOD BIOPSY
● Series of intrachromosomal recombination events mediated by recombinase enzymes
that recognize specific sequences flanking the gene segments
● Very common in immune cells, especially lymphocytes
Gene Rearrangements
Normal intrachromosomal breaking & joining of DNA in the genes coding for immunoglobulins and T-cell receptors
V(D)J recombination
● Gene encoding the immunoglobulin
heavy chain is located on chromosome
14
● As B lymphocytes mature, selected
gene segments are joined together so
that the rearranged gene contains only
1 of each V (variable). D (diversity) & J
(joining) gene segments
Immunoglobulin heavy-chain gene rearrangement in B cells
● Genes encoding the lg light chains:
kappa locus (chromosome 2) & lambda
locus (chromosome 22)
● Rearranged in a kappa-before-lambda
order
Immunoglobulin light-chain gene
rearrangement in B cells
● T-cell receptor: 2 of 4 chains (α, β. γ &
δ) with characteristic structures
resembling Ig V. J. & C regions
○ α & δ chains: chromosome 14
○ Β & γ chains: chromosome 7
● V regions undergo gene
rearrangement by intrachromosomal
recombination
● V. (D). & J segments are joined
together with the addition/deletion
(trimming) of nucleotides at the
junctions between the gene segments
T-cell receptor gene rearrangement
MUTATIONS IN HEMATOLOGICAL MALIGNANCIES:
- t(14;18)(q32;q21)
Detection methods:
● Southern Blot
● PCR or qPCR with gel
electrophoresis or qPCR probe
Follicular lymphoma
MUTATIONS IN HEMATOLOGICAL MALIGNANCIES:
- t(11;14)(q13;q32)
Detection methods:
● Southern Blot
● PCR and RT-PCR
with gel/capillary
electrophoresis
● FISH or flow
cytometry analysis
Mantle cell lymphoma,
chronic lymphocytic
leukemia, B-prolymphocytic
Teukemia, plasma cell
leukemia, multiple myeloma,
splenic lymphoma
MUTATIONS IN HEMATOLOGICAL MALIGNANCIES:
- t(8:14)(q24:q11)
Detection methods
● Southern blot, using a 32p or digoxigenin-
labeled 1.4 kb Cla1-EcoR1 restriction
fragment
● Interphase FISH & CISH
● IHC: Myc protein
expression
Burkitt lymphoma
MUTATIONS IN HEMATOLOGICAL MALIGNANCIES:
- t(15:17)(q22:q11.2-
q12)
- Fusion of the retinoic
acid receptor alpha
(RARA) gene on
chromosome 15 w/
the myelocytic
leukemia (MYL) gene
on chromosome 17
Detection Methods
● RT-PCR
● RT-qPCR
Promyelocytic
leukemia
