Genome Instability

Question 1

Causes of DNA damage

Answer 1

ionizing radiation
UV radiation
Chemicals
Spontaneous damage

Question 2

Genes associated to double-strand break signaling

Answer 2

ATM
MRE11
NBS1

Question 3

Inheritance and gene associated with Bloom’s Syndrome

Answer 3

AR; BLM

Question 4

bloom syndrome characteristics

Answer 4

prenatal and postnatal growth deficiency with normal body proportion
sun sensitivity
facial features (malar hypoplasia, nasal prominence , small mandible, dolichocephalic skull)
immune deficiency
sterile males, decreased fertility in females

Question 5

Individuals with Bloom syndrome are at an increased risk for (Cancer)

Answer 5

Carcinomas (small and large intestine, skin, GI, breast, genital and urinary tract, lower respiratory tract, liver)
Lymphoma
Leukemia

Question 6

BLM is associated with which protein in DNA replication

Answer 6

Helicase

Question 7

Cells that lack BLM function show

Answer 7

excessive chromosome breakage, increased sister chromatid exchange, increased exchange between homologous chromosomes

Question 8

What does BLM do during homologous recombination

Answer 8

dissolve Holliday junctions

Question 9

In Bloom’s syndrome there are _ rates of homologous recombination

Answer 9

higher

Question 10

Cancer surveillance for Bloom syndrome

Answer 10

abdominal US every 3 months beginning at diagnosis through 8 years for Wilms tumor
whole body MRI every 1-2 years beginning at age 12-13
annual colposcopy and biannual fecal test beginning at 10-12 years
breast MRI for women starting at 18
annual skin exam throughout life

Question 11

Causes of Fanconi Anemia

Answer 11

caused by mutations in 22 genes
most common: AR inheritance
RAD51: AD/ de novo
FANCB: X-LINKED

Question 12

Characteristics of Fanconi Anemia

Answer 12

aplastic anemia and/or bone marrow failure
prenatal and postnatal short stature
abnormal skin pigmentation
skeletal malformations (hypo-plastic thumb and/or radius)
microcephaly
heat defects
renal malformations

Question 13

Cancers associated to Fanconi Anemia

Answer 13

Acute myeloid leukemia
Head and neck squamous cell carcinoma
oral cavity
vulvar cancer
esophagus
GI tract
Anal Cancer

Question 14

Career frequency for FANC variants

Answer 14

1 in 180
>80% in FANCA, FANCG, FANCC

Question 15

What do Fanconi Anemia genes repair

Answer 15

DNA Interstand Crosslinks

Question 16

Management for patients with Fanconi Anemia

Answer 16

low dose androgens
hematopoietic stem cell transplantation
regular screening of the head and neck and no-genital region to screen for solid tumors
upper GI endoscopy

Question 17

Subtypes of Fanconi Anemia

Answer 17

BRCA2 (FANCD1): AR; early onset leukemia, medullloblatomas, Wilms tumor, 97% chance of cancer by age 6
PALB2 (FANCN) medulloblastomas and Wilms tumors
FANCG: severe bone marrow failure, higher incidence of leukemia