Pathology Flashcards
(98 cards)
Mutation of the ___ gene is the FIRST step in the classic adenoma-to-carcinoma sequence; it is found in most cases of SPORADIC colon cancer and in all patients with Familial Adenomatous Polyposis
APC tumor suppressor
The microsatellite instability pathway is characterized by mutations in DNA _____ genes (MLH1 and MSH2) and is implicated in the development of hereditary nonpolyposis colorectal cancer (Lynch syndrome).
mismatch repair
Aflatoxin exposure is associated with a G:C → T:A transversion in the p53 gene, which greatly increase the risk of developing _____ carcinoma.
hepatocellular
Osteosarcomas typically form when a mesenchymal stem cell develops mutations in the following genes:
RB & TP53
Tumor Supressor Genes
Activating mutations of ___ are responsible for most cases of hairy cell leukemia & Melanomas
BRAF
Activating mutations in the ___ proto-oncogene are common in colorectal cancer and non-small cell lung cancer. It encodes for a GTPase that relays cellular growth and proliferation signals from outside the cell.
KRAS
Germ-line mutations of the ___ proto-oncogene cause multiple endocrine neoplasia type 2
RET
most common primary bone malignancy in children and young adults. It occurs most frequently at the metaphyses of long bones and presents with local pain and swelling. Most cases are associated with sporadic or inherited mutations in RB1 (hereditary retinoblastoma) and TP53 (Li-Fraumeni syndrome).
Osteosarcoma
TP53 tumor suppressor gene, which encodes for P53, a protein that regulates cell-cycle progression and maintains genomic integrity by activating DNA repair following damage. Germ-line mutations are associated with ___ syndrome
Li-Fraumeni syndrome
In humans, ____ is concentrated in liver cells; elevated levels suggest an obstructive biliary process.
alkaline phosphatase
zinc-containing enzymes that degrade/penetrate components of the extracellular matrix (ECM) and basement membrane
Metalloproteinases
Tumor Cell Invasion:
Tumor cells detach from surrounding cells (↓cadherins)
Tumor cells adhere to the basement membrane (↑laminin)
Tumor cells invade the basement membrane (metalloproteinases)
Detach
Adhere BM
Degrade BM
BRCA1 and BRCA2 in particular are involved in repair of double-stranded ___. A mutation increases the risk of developing breast and ovarian cancer.
DNA breaks
Epidermal growth factor receptor (EGFR) stimulation leads to downstream activation of ___, a membrane-bound GTP-binding protein that stimulates cellular growth and proliferation.
KRAS
stimulation leads to downstream activation of KRAS, a membrane-bound GTP-binding protein that stimulates cellular growth and proliferation.
Epidermal growth factor receptor (EGFR)
Epidermal growth factor receptor (EGFR) stimulation leads to downstream activation of KRAS, a membrane-bound ___-binding protein that stimulates cellular growth and proliferation.
GTP
Unchecked cellular growth via overexpressing ___ or by developing constitutive activating mutations in the ___ proto-oncogene.
EGFR
KRAS
Lipopolysaccharides trigger the degradation of __ inhibitor protein allowing it to release NFkB so it can enter the nucleus and stimulate the transcription of cytokines like TNF alpha and IL-1
IkB
Janus kinase 2 (JAK2) is a non- receptor tyrosine kinase involved in the signaling pathway for myeloproliferation. Constituent activation is associated with ___ disorders.
primary myeloproliferative
The principal protein that stimulates the production and release of neutrophils from the bone marrow.
Granulocyte colony-stimulating factor (G-CSF)
An essential step in the MHC I processing of a virus is the breakdown of intracellular viral proteins by the ___ pathway.
ubiquitin proteasome
The key growth factors that promote ___ in neoplastic and granulation tissue are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF).
angiogenesis
The key growth factors that promote angiogenesis in neoplastic and granulation tissue are __ & __
vascular endothelial growth factor (VEGF)
fibroblast growth factor (FGF)
Require gain-of-function mutations to become cancerous. They typically encode proteins that promote cell division (eg, growth factors, receptors, signal transduction factors). Only one allele must be damaged to increase the risk of cancer formation.
Protooncogenes (RET)
