Intro to Neoplasia II (Putthoff Lect) Ch 7 Flashcards
Describe the changes in grading you would observe in various stages of cervical cancer
CIN I (Cervical intraepithelial grade 1) = Start to see a proliferation of cells above the basement membrane,however there is still a maturation process that can be seen
CIN I (Cervical intraepithelial grade 2) = Even more disordered proliferation than grade 1
CIN (Cervical intraepithelial grade 3) = NO MATURATION process is observable
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What are these examples of?
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Basal cell carcinomas
The coarse chromatin feature seen in cancerous cells is due to…
HETEROCHROMATIN
*Remeber: It is dense and inactive
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Describe the concept of differentiation
The degree to which a neoplasm resembles the tissue from which it arises or is derived
What is the major general rule to follow for differentiation of tissue?
The less differentiated a malignant neoplasm, the more aggressive it’s biological behavior
What are some examples of well differentiated benign tumors?
Leiomyoma
Thyroid adenoma
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What is the grading system for malignant neoplasms?
Well differentiated
Moderatley differentiated
Poorly differentiated
Undifferentiated
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What are general characteristics of benign neoplasms?
- Resemble the tissue of origin
- Well differentiated
- Likely to retain functions of their cells of origin
- Slow growing
- Circumscribed, may have a capsule
- Remain localized at the site of origin
What are general characteristics of malignant neoplasms?
-Undifferentiated
-Sometimes aquire unexpected functions
-Faster growing
- Poorly circumscribed, tend to invade surrounding normal tissues
- Have capability to metastasize to distant sites
What is the ABSOLUTE only criteria for malignancy?
METASTASIS
INCLUDE KEY CONCEPTS on page 274 here
What are examples of cavitary lung lesions?
Bronchogenic carcinoma
Staphylococcal pneumonia
Fibro-caseous cavitary TB
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What is a good GENERAL rule to follow when it comes to naming a neoplasia that is either benign or malignant?
Benign = -oma
Malignant = -sarcoma
*Remember. This is not a hard rule. Just GENERALLY a lot of malignant cancers have -sarcoma, however they can have -oma at the end. Haven’t seen a benign tumor with -sarcoma at the end though!
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There is no such thing as a benign ______ tumor
Wilms
Describe the comparison b/w cancer indidence and cancer deaths between men and women
Incidence: Men (Prostate most common) Women (Breast most common)
Deaths: Men (Lung most common) Women (Lung most common)
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The vast majority of cervical cancers arise from?
HPV
(considered a sexually transmitted cancer)
Cervical cancer
What type of cancer?
Squamous cell cancer
INSERT KEY CONCEPTS on pg 280 for epidemiology of cancer here
Describe development of a tumor
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Clinically, how big and how many cells does a tumor contain to allow us to identify it?
Mass of 1 gram
1 billion cells (10^9)
_____________ can explain not only the natural history of cancer, but also changes in tumor behavior following therapy
Selection of the fittest cells
What is one of the most profound selective pressures that cancer cells face?
Effective chemo/radiotherapy given by the treating physicians
What are the 4 classes of regulatory genes?
Growth-promoting proto-oncogenes
Growth-inhibiting tumor-suppressor genes
Genes that regulate apoptosis
DNA-_repair genes_
How many alleles need to be converted to induce neoplasia for:
Proto-oncogene
Tumor suppressor gene
Proto-oncogene = will become an oncogene if ONE of the two alleles is converted
Tumor suppressor gene = will promote neoplasia ONLY IF BOTH alleles are converted. Having one of the two gene products is sufficient to inhibit neoplasia
What type of modifications include:
DNA methylation
Histone modifications
Epigenetic modifications
What is the effect of DNA methylation on gene expression?
Silence gene expression
What are examples of proto oncogenes that are categorized as growth factor receptors?
EGF
ALK
What are examples of proto oncogenes that are categorized as proteins involved in signal transduction?
RAS
ABL
BRAF
SHH/WNT
What is an example of a proto oncogene that is categorized as a nuclear regulatory protein?
MYC
What is the most common type of abnormality involving proto-oncogenes in human tumors?
RAS mutations
What pathway is crucial for the development of the bilaterian feature of humans?
The Hedgehog (HH signaling) pathway
along with one of its key regulators (Sonic SHH)
General rule for the term blastoma?
Generally its a familial cancer seen in pediatric pop’n
Which proto-oncogene is VERY important and involved in nearly all human tumors?
MYC
What is the general description of MYC?
A major transcriptional regulator of cell growth
It activates many of the genes that are involved in cell growth
What is a unique feature of MYC?
Can act to reprogram somatic cells into pluripotent stem cells
INSERT KEY CONCEPTS PAGE on MYC Oncogene pg 290 here
What are the two major tumor suppressor genes?
p53
Rb
Table 7-7
What are the inhibitors of mitogenic signaling pathways?
APC (AD)
NF1 (AD)
NF2 (AD)
PTCH
Table 7-7
What are the inhibitors of cell cycle progression?
RB (AD)
Table 7-7
What are the inhibitors of pro-growth programs of metabolism and angiogenesis?
VHL (AD)
Table 7-7
What are the inhibitors of invasion and metastasis?
CDH1
(E-cadherin)
Table 7-7
What are enablers of genomic stability?
TP53 (AD)
Table 7-7
What are the DNA repair factors?
BRCA1
BRCA2
MSH (AR)
What is referred to as the “gaurdian of the genome”?
ALSO is the most frequently mutated gene in human cancers
p53
What is aka “gatekeeper of colonic neoplasia”?
APC
What is related to certain CNS tumors, renal cysts, neuroendocrine tumors and renal cell carcinoma?
VHL
What is commonly known as the “governor of the cell cycle”?
RB
What is the difference b/w familial and sporadic RB mutations?
Familial = children inherit one defective copy of the RB gene in the germline (the first hit), and the other copy is normal. Retinoblastoma develops when the normal RB allele is mutated as the result of a spontaneous somatic mutation.
Sporadic= Both normal RB alleles must undergo somatic mutation in the same retinoblast (two hits). The probability of this occuring is LOW!
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What chromosome and where on the chromosome is p53 found?
Chromosome 17p13.1
What happens with a loss of p53 function?
- DNA damage goes unrepaired
- Driver mutations accumulate in oncogenes
- Cell is on a dangerous path leading to malignant transformation
Loss of p53 is heavily associated with which particular syndrome mentioned in class?
Li-Fraumeni syndrome
Where is WT1 found?
Chromosome 11p13
What is loss of WT1 associated with forming?
Wilms tumor
Pediatric kidney cancer
*WT1 was named for the disease it causes when it’s non-functional! WT=Wilms tumor
What is a major immunotherapy mechanism used to treat cancer?
Use of monoclonal antibodies that target either PD-1/PD-L1/CTLA-4
This will boost the immune response to cancer cells
Describe the concept of angiogenesis in cancer formation
Development of blood supply to the newly formed mass
Table 7-8
State the translocation
Chronic myelogenous leukemia (CML)
(9;22) (q34;q11)
Table 7-8
State the translocation
Acute myeloid leukemia (AML)
(8 ; 21) (q22 ; q22)
(15; 17) (q22 ; q21)
Table 7-8
State the translocation
Burkitt lymphoma
(8 ;14) (q24; q32)
Table 7-8
State the translocation
Mantle cell lymphoma
(11 ; 14) (q13 ; q32)
Table 7-8
State the translocation
Follicular lymphoma
(14, 18) (q32, q21)
What are the most frequent radiation induced cancers?
Myeloid leukemias
Microbial carcinogenesis
What is the ONE oncogenic RNA virus?
HTLV-1
Microbial carcinogenesis
What are examples of Oncogenic DNA viruses?
HPV
EBV
HBV
Merkel cell polyomarvirus (MCV)
HHV-8
What are paraneoplastic syndromes?
Tumor cells themselves elaborate certain substances that have effects
What is the most common paraneoplastic syndrome?
Endocrinopathy
What is chromothripsis?
Widespread chromosomal issues are occuring with cancer
“Genome instability characterized by tens to hundreds of locally clustered rearrangements affecting one or more chromosome(s) in cancer cells. This phenomenon, is likely due to a single catastrophic event leading to the simultaneous formation of multiple double-strand breaks, which are repaired by error-prone mechanisms”
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WOOOOOOOOOOO