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 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
