neoplasia Flashcards
What does monoclonal mean in neoplasia?
Neoplastic cells are derived from a single mother cell.
How is clonality historically determined?
By analyzing glucose-6-phosphate dehydrogenase (G6PD) enzyme isoforms.
What is the normal ratio of G6PD isoforms in polyclonal tissues?
1:1
What is the difference in G6PD isoform ratio between hyperplasia and neoplasia?
Hyperplasia is polyclonal (1:1 ratio), while neoplasia is monoclonal (only one isoform).
How is B lymphocyte clonality determined?
By analyzing the immunoglobulin (Ig) light chain phenotype (kappa or lambda)
What is the normal kappa to lambda light chain ratio in B cells?
3:1.
How does the kappa to lambda ratio change in lymphoma?
The ratio becomes >6:1 or is inverted (e.g., 1:3), indicating monoclonality.
What distinguishes benign tumors from malignant tumors?
Benign tumors: Localized, do not metastasize.
Malignant tumors: Invade locally and can metastasize
What determines tumor nomenclature?
The lineage of differentiation (type of tissue) and whether the tumor is benign or malignant.
How many cell divisions occur before the earliest clinical symptoms of cancer?
Approximately 30 divisions.
What does a Pap smear detect?
Cervical dysplasia (CIN) before it becomes carcinoma
What does mammography detect?
In situ breast cancer (e.g., DCIS) before it invades.
Invasive carcinoma before it becomes clinically palpable
What are carcinogens?
Agents that damage DNA, increasing cancer risk (e.g., chemicals, viruses, radiation)
What are proto-oncogenes?
Genes essential for cell growth and differentiation. Mutations form oncogenes, leading to unregulated cellular growth.
What are the categories of oncogenes?
Growth factors (e.g., PDGFB in astrocytoma)
Growth factor receptors (e.g., HER2/neu in breast cancer)
Signal transducers (e.g., ras)
What cancer is associated with aflatoxins?
Hepatocellular carcinoma
Derived from Aspergillus, which can contaminate stored rice and grains.
What cancer is caused by alkylating agents?
Leukemia/lymphoma.
Side effect of chemotherapy
Name three cancers associated with alcohol.
Squamous cell carcinoma of oropharynx and upper esophagus
Hepatocellular carcinoma
What cancers are linked to arsenic exposure?
Squamous cell carcinoma of skin
Lung cancer
Angiosarcoma of the liver
Arsenic is present in cigarette smoke.
What cancers are associated with asbestos?
Lung carcinoma
Mesothelioma
Exposure to asbestos is more likely to lead to lung carcinoma than mesothelioma.
What cancer is caused by naphthylamine?
Urothelial carcinoma of the bladder.
Derived from cigarette smoke.
What cancer is linked to nitrosamines?
Stomach carcinoma.
What cancer is caused by naphthylamine?
Urothelial carcinoma of the bladder
What cancer is associated with vinyl chloride?
Angiosarcoma of the liver.
Occupational exposure; used to make PVC for pipes.
What cancers are linked to exposure to nickel, chromium, beryllium, or silica?
Lung carcinoma.
What cancers are associated with EBV (Epstein-Barr Virus)?
Nasopharyngeal carcinoma
Burkitt lymphoma
CNS lymphoma in AIDS
What cancer is linked to HHV-8?
Kaposi sarcoma.
What cancer is linked to HTLV-1?
Adult T-cell leukemia/lymphoma.
Which high-risk HPV subtypes are associated with cancer?
Subtypes 16, 18, 31, 33.
Causes squamous cell carcinoma of vulva, vagina, anus, and cervix; adenocarcinoma of the cervix.
What cancers are associated with ionizing radiation?
AML (Acute Myeloid Leukemia)
CML (Chronic Myeloid Leukemia)
Papillary carcinoma of the thyroid
Generates hydroxyl free radicals.
What cancers are linked to non-ionizing radiation (e.g., UV sunlight)?
asal cell carcinoma
Squamous cell carcinoma
Melanoma of the skin
Results in the formation of pyrimidine dimers in DNA, normally excised by restriction endonuclease.
What is the inactive state of ras?
Ras is associated with growth factor receptors in an inactive GDP-bound state.
How is ras activated?
Receptor binding causes GDP to be replaced with GTP, activating ras.
Activated ras sends growth signals to the nucleus.
How does ras return to its inactive state?
Ras inactivates itself by cleaving GTP to GDP; this process is augmented by GTPase activating protein.
What happens in ras mutations?
Mutated ras inhibits the activity of GTPase activating protein, prolonging the activated state of ras and increasing growth signals
What is the role of cyclins and cyclin-dependent kinases (CDKs)?
Cyclins and CDKs form a complex that phosphorylates proteins, driving the cell through the cell cycle.
Give an example of a cyclin-CDK complex and its function.
The cyclin D/CDK4 complex phosphorylates the retinoblastoma (Rb) protein, promoting progression through the G1/S checkpoint.
What is the role of tumor suppressor genes?
Tumor suppressor genes regulate cell growth and decrease the risk of tumor formation
Name two classic tumor suppressor genes.
p53 and Rb (retinoblastoma).
What is the function of p53?
p53 regulates the progression of the cell cycle from G1 to S phase.
What is the function of PDGFB and its associated tumor?
Function: Platelet-derived growth factor.
Mechanism: Overexpression, autocrine loop.
Associated Tumor: Astrocytoma.
What tumor is associated with ERBB2 (HER2/neu) and its mechanism?
Function: Epidermal growth factor receptor.
Mechanism: Amplification.
Associated Tumor: Subset of breast carcinomas.
What is the role of RET and its associated conditions?
Function: Neural growth factor receptor.
Mechanism: Point mutation.
Associated Tumors: MEN2A, MEN2B, and sporadic medullary carcinoma of the thyroid.
What type of tumor is linked to KIT and its mechanism?
Function: Stem cell growth factor receptor.
Mechanism: Point mutation.
Associated Tumor: Gastrointestinal stromal tumor.
What are the key features of the RAS gene family?
Function: GTP-binding protein.
Mechanism: Point mutation.
Associated Tumors: Carcinomas, melanoma, and lymphoma.
What is the significance of ABL in oncogenesis?
Function: Tyrosine kinase.
Mechanism: t(9;22) translocation with BCR.
Associated Tumors: Chronic myeloid leukemia (CML) and some types of acute lymphoblastic leukemia (ALL).
What tumor is associated with c-MYC, and what is the genetic alteration?
Function: Transcription factor.
Mechanism: t(8;14) involving IgH.
Associated Tumor: Burkitt lymphoma
What tumor is associated with N-MYC?
Function: Transcription factor.
Mechanism: Amplification.
Associated Tumor: Neuroblastoma.
What tumor is associated with L-MYC?
Function: Transcription factor.
Mechanism: Amplification.
Associated Tumor: Small cell lung carcinoma.
What is the function of CCND1 (Cyclin D1) and its associated cancer?
Function: Cyclin.
Mechanism: t(11;14) involving IgH.
Associated Tumor: Mantle cell lymphoma.
What tumor is associated with CDK4 and its mechanism?
Function: Cyclin-dependent kinase.
Mechanism: Amplification.
Associated Tumor: Melanoma.
