L14 cancer predisposition syndromes

Question 1

clinical phenotype of fanconi anaemia

Answer 1

microcephaly
mental retardation
developmental delay- stunted growth
aplastic anaemia
predisposition to cancer
bone marrow failure

Question 2

chromosome hypersensitivity to dna inter-strand cross links leads to deformed chromsomes- what forms can they go into?

Answer 2

chromosome gaps/ breaks
tri-radial chromsomes
quadra-radial chromosomes
complex chromsomal rearrangement

Question 3

what is the genetic basis of FA?

Answer 3

need homozygous mutations
fanca, fanc, fancg make up 85% of all cases

Question 4

what cancers do they develop?

Answer 4

MDS then develops into AML
older patients with bone marrow transplants= head and neck and gastro cancers
carriers of brca1/ 2/ palb2= breast/ ovarian cancer
biallelic mutations in fancd1= AML, T-ALL, GBM

Question 5

how does genomic instability caused by icl repair cause mitotic catastrophe?

Answer 5

icl= unreplicated dna= forms hemicatenated DNA
anaphase bridge forms when chromtids try separate
chromosome breakage
formation of multi-radial chromosomes
form micronuclei
cell divides again= loss of genetic info
keeps happening= mitotic catastrophe

Question 6

how would NHEJ inhibition help formation of radial chromosomes?

Answer 6

icl= dna breaks
mis-repaired by nhej
leads to chromosome fusions= toxic when cells undergo mitosis as leads to mitotic catastrophe

Question 7

which clinical phenotypes did FA-/- mice present and not present with?

Answer 7

present- hypersensitivity to MMC
chromosomal instability
developmental abnormalities

not present- progressive bone marrow failure