Neoplasia (Day 2) Flashcards
What are the four classes of regulatory genes?
- Activation of growth promoting oncogenes
- Inactivation of tumor suppressor genes
- Regulation of apoptosis
- DNA repair genes
How can tyrosine kinase be constantly activated through?
- Point mutations (most common in elderly carcinomas)
- Gene rearrangements
- Gene amplification (over-expression)
If an epidermal growth factor receptor family (EGFR/ERBB) is inactivated, what happens?
- Neurodegenerative Multiple Sclerosis
- Alzheimer’s
If an epidermal growth factor receptor family (EGFR/ERBB) is activated, what happens?
ERBB2 is also called Her2/Neu
- Breast Cancer (ERBB2/Her2Neu)
- Lung Adenocarcinoma (ERBB1)
- Stomach, Ovarian, or Uterine Cancer
What is an important tyrosine growth factor receptor for breast, lung, brain, and the stomach?
Fibroblastic Growth Factor Receptor
What is an important tyrosine kinase receptor for tumor angiogensis?
Vascular Endothelial Growth Factor (VEGFR)
What is an important tyrosine kinase receptor for familial medullary thyroid carcinoma (MEN2A & MEN2B)?
RET Receptor
Conversion of proto-oncogenes to oncogenes occurs by what three mechanisms?
- Point mutations
- Translocations
- Amplification (Over-expression)
What is an endometrial carcinoma downstream tyrosine kinase mutation?
PTEN (suppressor)
What is a breast carcinoma downstream tyrosine kinase mutation?
P13K
What is a “Hairy cell leukemia/Melonoma” downstream tyrosine kinase mutation?
RAF/BRAF
What types of mutations create fusion genes encoding constitutively active tyrosine kinases?
- Chromosomal Translocations
- Rearrangements
Explain how Chronic Myelogenous Leukemias (CML) and some Acute Lymphoblastic Leukemias (ALL) are mutated?
Chromosome 9 ABL gene is translocated to chromosome 22 (and fuses to the BCR gene).
What translocation events lead to over-expression of proto-oncogenes?
- t (8;14) Burkitt Lymphoma (c-MYC)
- t (14;18) Follicular Lymphoma (Bcl-2)
What translocation events create a fusion/chimeric gene (where the product promotes cell proliferation in the same manner as an oncogene)?
- t (9;22) Chronic Myeloid Leukemia
- t (15;17) Acute Promyelocytic Leukemia (AML M3)
- t (11;22) Ewing Sarcoma
What is Renal Cell Carcinoma and Alveolar Soft Parts Sarcoma translocation?
Xp11 (X:17)
What is Synovial Sarcoma translocation?
X:18
Explain CML’s mutation error.
BCR is bound to ABL1 = “Philadelphia Chromosome” (leads to tyrosine kinase activation)
Explain Burkitt Lymphoma’s mutation error.
c-MYC translocation with an immunoglobin heavy chain > lymphocyte proliferation and possible amplification (worse prognosis with amp)
Explain Follicular Lymphoma mutation error.
Bcl-2 inhibits apoptosis, which leads to over-expression.
Explain Acute Promyelocytic Leukemia mutation error.
PML is bound to RAL alpha, which is a transcription factor.
Explain Synovial Sarcoma mutation error.
SYT is bound to SSX
Explain Ewings Sarcoma mutation error.
EWS is bound to FLI1, which is a transcription factor.
What oncogene does EGFR encode for?
ERBB1/HER1
What oncogene does EGFR2 encode for?
ERBB2/HER2
What oncogenes does GTPase encode for?
H-RAS and K-RAS
What oncogenes does TK encode for?
BCR-ABL and SRC
What does tumor suppressor gene p53 regulate?
- Cell cycle progression
- DNA repair
- Cellular senescence
- Apoptosis
What is the gatekeeper for chronic neoplasia?
APC (Adenomatous Polyposis Coli)
If a person has a mutation in APC, what happens?
They will likely develop Familial Adenomatous Polyposis (FAP) > 100% of Colon Cancers
What gene causes Retinoblastoma and Osteosarcoma tumors?
Rb
What gene causes lung, colon, and breast caner?
p53
What gene causes Hereditary breast and ovarian cancer?
BRCA-1
What gene causes Hereditary breast cancer (alone)?
BRCA-2
What gene causes Adenomatous polyps and colon cancer?
APC
What gene causes Neurofibromas?
NF-1
