Cancer syndromes & treatment side-effect syndromes Flashcards
LFS
autosomal dominant, mutated p53 = loss of apoptosis, loss of DNA repair, much higher risk of cancer
Lynch syndrome
defective MMR causes genomic instability, increases chance for colon/endometrial cancers.
CML
driven by ABL-BCR/ Philadelphia chromosome translocation - Chr.9>22.
RTK always on = proliferation
AML
can treat with IDH inhibitors, but the treatment may cause differentiation syndrome
tumor lysis syndrome
Can occur spontaneously or when a pt with hematological cancer is treated with PARP/Bcl2 inhibitors. The increased apoptosis of blood cells causes increase in free nucleotides that leads to uric acidemia, renal insufficiency, seizures.
Neuroblastoma
usually childhood cancer (<2 years old). Caused by MYCN intrachromosomal amplification
Retinoblastoma
Proof of 2 hit hypothesis -> in familial cases, one copy of the mutant RB gene is inherited. The patient develops retinoblastoma only when the other normal RB copy is lost by somatic mutation. Normal RB is dominant.
Childhood eye tumor caused by loss of RB tumor suppressor = loss of growth arrest and DNA repair, increased transcription/proliferation and mutations.
xeroderma pigmentosum
defective NER pathway causes increased skin cancer incidence.
differentiation syndrome
side effect of treatment of AML with IDH inhibitors, dangerous cytokine storm/inflammation
genomic instability
can be due to hereditary mutations or due to loss of p53/RB which causes loss of DNA repair in the cell cycle. Defective DNA repair causes instability which increases cancer risk by increasing gene amplificationm chromosomal translocations, and other mutations.
Ex: Lynch, Xeroderma, LFS (loss of p53), BRCA1/2 in breast cancer
familial adenomatous polyposis (FAP)
increased risk for colon cancer, caused by loss of both copies of the APC allele = increased wnt signaling = uncontrolled growth/proliferation.
