CBCL 3 Pre-Work Flashcards
The protein product of the Bcl-2 gene functions as a tyrosine kinase
Protects cells from the mitochondrial apoptosis pathway
Inherited mutations in this tumor suppressor gene are found in familial adenomatous polyposis (FAP)
Inherited APC mutations are found in most patients with familial adenomatous polyposis. Inherited MSH2 mutations are associated with hereditary non-polyposis colon cancer.
A reciprocal translocation between chromosomes 9 and 22 produces a chimeric gene including this tyrosine kinase, and is implicated in the pathogenesis of chronic myeloid leukemia and some cases of acute lymphoblastic leukemia.
The ABL gene on chromosome 9 fuses with the BCR gene on chromosome 22 due to t(9;22) (Philadelphia Chromosome) in CML and some cases of ALL. The chimeric gene produces a novel protein that contains the tyrosine kinase domain of ABL and is overexpressed in the affected cells.
A benign neoplasm arising from uterine myometrial smooth muscle is called?
Leiomyoma. Smooth muscle tumors are given the prefix ‘leio-‘. A benign neoplasm is given the suffix ‘-oma’. Hence, ‘leiomyoma’.
The presence of keratin pearls in a malignant neoplasm arising from the larynx identifies it as a(n)
Squamous cell carcinoma. The presence of keratinization identifies the cell/tissue of origin as squamous epithelium. Since it is a malignant neoplasm, the correct diagnosis is squamous cell carcinoma.
Which of the following features is most helpful in distinguishing a malignant neoplasm from a benign neoplasm?
Invasion. Invasion and metastasis are unique features of malignant neoplasms, not seen in benign neoplasms. Other features listed can be seen to various degrees in both benign and malignant neoplasms.
A diagnosis of cervical intraepithelial neoplasia (CIN) indicates
Epithelial dysplasia. Intraepithelial neoplasia is a synonym for dysplasia. Epithelial dysplasia indicates neoplastic transformation, but the neoplastic proliferation is limited to the epithelium, without invasion through the basement membrane.
Which of the following is a tumor suppressor gene?
RB is a tumor suppressor gene. The rest are oncogenes that work through gain of function mutations.
Gene amplification is the mechanism of overactivation of this oncogene in some cases of breast cancer.
ERB-B2, also called Her-2/neu, is overactivated in some cases of breast cancer by gene amplification. These patients may benefit from treatment with a monoclonal antibody that targets Her-2/neu, trastuzumab.
A 1.5 cm fungating mass is biopsied from the cervix of a 38 year old woman. What is the best diagnosis?
Squamous cell carcinoma. There are invasive islands of epithelial cells with evidence of keratinization [left], indicative of squamous differentiation. The best diagnosis is squamous cell carcinoma.
Activation of oncogenes requires what mutation?
Gain of function mutation
What are the two types of GOF mutations that lead to the activation of an oncogene?
Change in structure of proto-oncogenes leading to hyperactivity and function different than that of original
Change in gene expression - structurally they are the same, but they can be produced at the wrong time, in large quantities, or for very long periods of time.
How many alleles need to be affected to result in a neoplasia for an oncogene vs a tumor suppressor?
An oncogene need a mutation on only a single allele to result in a neoplasia, and a tumor suppressor needs inactivating mutations in both alleles to result in a neoplasia.
How do growth factors work as an oncogene?
Growth factors can be produced by cancer cells and set up an autocrine loop. They also work on nearby cancer cells. GF that are secreted into the body an work systemically are not very good oncogenes because they would have a varying diffuse effect and would not be able to affect any individual cells, as would be needed for transformation.
How does a growth factor receptor work as an oncogene?
If a Growth Factor Receptor is mutated and becomes hyperactive, it can have direct effect on a single cell and can lead to transformation
What is a common receptor effor leading to breast cancer?
Overexpression of ERB-B2 (HER-2/neu EGF receptor)
How can ERB-B1 (EGFR) be related to lung cancer?
A point mutation can lead to a loss of normal function with is prominent in lung cancer
Give a common example of GTP-binding proteins (G proteins) involvement in neoplasms.
Activation of G-protein pathways by RAS point mutations in many neoplasms (most common abnormality of oncogenes in human cancer)
How is activation of ABL in chronic myelogenous leukemia achieved?
In this leukemia, ABL gene on chromosome 9 is translocated on chromosome 22 and fuses with the BCR on chromosome 22.
How does the BCR/ABL translocation lead to cancers?
BCR is always constitutively active, so when fusion occurs, the complex is also constitutively active and expressed, which causes cell proliferation. The chimeric protein acts as an oncoprotein in this leukemia
What is the role of C-MYC in Burkitt lymphoma?
Burkitt Lymphoma is a B-Lymphocyte malignancy. C-MYC overexpression due to t(8;14). All B lymphocytes make immunoglobulin protein so the immunoglobulin protein on chrom.14 is constantly expressed. The translocation from chromosome 8 will lie right before the promoter region on chrom.14 and will be constitutively active, causing constant production of C-MYC, causing neoplastic transformation
What is the role of N-MYC in neuroblastoma?
overexpression in neuroblastoma due to gene amplification (instead of one copy on the chromosome, there are multiple copies on the same chromosome, which contain the N-MYC gene and can be recognized by karyotyping.Can detect fragments (doubleminutes) or long areas of the chromosome that have the same staining characteristic because it’s the same gene being repeated over and over again.
What are some important cell cycle regulators involved in cancer?
Cyclin D1 overexpression in mantle cell lymphoma CDK4 amplification in melanoma, glioblastoma
What is the role of a tumor suppressor gene?
Prevent inappropriate cell division and cell growth
What are the two mechanisms in which a loss of function can occur of a tumor suppressor?
Inactivation of both alleles (inactivation of only one allele is silent)
Inactivation of protein product
What is the importance of retinoblastoma Rb as a tumor suppressor gene?
Retinoblastoma (Rb) (chr.13)
Normal Rb protein (p105Rb) inhibits transcription by binding transcription factor E2F
Most critical checkpoint in the cell cycle Release of E2F allows G1-S phase transition
Mechanisms of release of E2F
Phosphorylation of p105Rb by activated cyclin/CK complex
Inactivation of p105Rb by products of oncogenic DNA viruses Loss of p105Rb
What is the role of (T)P53 as a tumor suppressor?
assess degree of DNA damage and cause the cell to undergo apoptotic cell death if’s not able to repair the damage
What are some causes for upregulation of p53?
upregulated by DNA damage, hypoxic stress, unregulated oncogene expression
Accumulation of p53 leads to what?
Cell cycle arrest at G1/S checkpoint (transient) or senescence or apoptosis Activation of genes involved in DNA repair
Oncogenic DNA viruses can have what effect on p53?
Inactivation of p53 protein by products of oncogenic DNA viruses
What is the normal function of APC?
Normal APC binds and inhibits β-catenin; prevents activation of transcription factors by β-catenin (part of WNT signaling pathway)
Abnormalities in the APC/β-catenin pathway implicated in?
Familial adenomatous polyposis coli
Sporadic colorectal cancer and other neoplasms
Why are tumors with TP53 mutations tricky?
Relatively resistant to chemotherapy and radiation (cells just don’t die) Mutator phenotype
What is the tumor parenchyma?
consists of neoplastic cells within tumor mass
What is the reactive stroma?
non-neoplastic connective tissue, blood vessels, immune cells, etc. within the tumor massf
What is dysplasia?
disordered growth of neoplastic epithelial cells, confined by the basement membrane
- Loss of uniformity of individual cells
- Loss in architectural orientation (polarity)
- Synonym: Intraepithelial Neoplasia (IN)
- Classified by degree of morphologic atypia
What is carcinoma in situ?
highest grade of dysplasia with all the cellular features of carcinoma but still confined by the basement membrane
Will all dysplasias become carcinomas?
No they can spontaneously correct if bodies regulatory mechanisms kills them off.
What are the important characteristic of either of these images?
Left: Can see lower magnification showing full thickness atypia of the squamous epithelium. Cells are enlarged, crowded, with darker and larger nuclei, making the entire area look much darker than normal.
Right: higher magnification, can see individual cells varying in size and shape, as well as numerous mitotic figures. Basement membrane is still in tact
What is the meaning of differentiation?
degree of resemblance (morphologic and biochemical) of neoplastic cells to the cell of origin.
What are the two contexts that differentiation is used in regards to benign and malignant neoplasms?
1) Benign neoplasms usually look more like their parent tissue than malignant neoplasms. Therefore benign neoplasms tend to be better differentiated than malignant neoplasms
2) Use the word differentiation to grade malignant neoplasms . Malignant neoplasms have a variety of appearances and neoplasms arising from the same type of tissue sometimes look very much like the parent tissue and sometimes don’t. This distinction is termed grading.
What is pleomorphism?
variation in size and shape of cells within the neoplasm
What is anaplasia?
lack of differentiation , presence of highly atypical cells in the neoplasm
What is a mixed tumor?
neoplasm with divergent differentiation (as cells acquire various abnormalities that cause them to transform neoplastically and proliferate without responding to controls (autonomous proliferation) , they can acquire ability to change their type of differentiation.
What is a teratoma?
neoplasm of germ cells with derivatives of different germ layers
What is invasion?
growth of neoplastic cells beyond the site of origin
What is metastasis?
discontinuous spread of neoplastic cells to a site distant from the site of origin
What are the general features of a benign tumor?
Localized
Incapable of invasion into
surrounding tissue
Incapable of metastasis
Good clinical
behavior/prognosis*
What is an adenoma?
Neoplasm of gland forming epithelium
What is a chondroma?
Benign tumor of cartilage tissue
What is a lipoma?
Benign tumor of adipose tissue
What is a leiomyoma?
Benign tumor of smooth muscle
What are the characteristics of malignant neoplasms?
Capable of invasion into surrounding tissue
Capable of metastasis
Bad clinical
behavior/prognosis*
Death most often due to
metastatic spread
Epithelial malignant tumors have what naming?
“-Carcinoma”
Ex. Adenocarcinoma, squamous cell carcinoma, renal cell carcinoma
Mesenchymal malignant tissues have what naming?
“-sarcoma”
Ex. Chondrosarcoma, liposarcoma, leiomyosarcoma (smooth muscle)
What is the exception to the naming rule?
Melanoma - is a malignant tumor
