Targeting Homologous Recombination Repair in Cancer - DNA Repair in Cancer Therapy - page 124

TABLE 7.1 Human Cancer Predisposition Syndromes with Known or Likely HRR Alterations

Syndrome Mutated gene(s) Phenotype

Fanconi anemia (FA) FANCA-C, D1, D2, E-G, I, J, L-N, P

(bi-allelic mutations, or X-linked
(FANCB))

Cancer:
AML, myelodysplasia, squamous cell carcinoma
Progeria:
Bone marrow failure
Neurological defects:
Microcephaly
Immunodeficiency:
Pancytopenia
Other:
Abnormal skin pigmentation,
infertility, limb deformities, renal dysfunction

Fanconi anemia-like
disorder

RAD51C
(bi-allelic mutations)

Cancer:
Not observed
Progeria:
Growth defects
Other:
Hypogonadism, limb deformities, renal dysfunction

Familial breast cancer ATM, BRCA1, BRCA2/FANCD1, BRIP1/

FANCJ, Chk2, NBS1, p53, PALB2/
FANCN, PTEN, RAD50, RAD51C
(heterozygous mutations)

Cancer:
Breast cancer, ovarian cancer

Bloom syndrome (BS) BLM

(bi-allelic mutations)

Cancer:
Carcinomas, leukemias, lymphomas
Neurological defects:
Microcephaly, mild mental retardation
Infertility
Other:
Abnormal skin pigmentation, facial dysmorphism,
immunodeficiency, growth defects

Rothmund Thomson
Syndrome (RTS)

RECQL4
(bi-allelic mutations)

Cancer:
Osteosarcoma, skin cancers
Progeria:
Cataracts, gray hair
Other:
Skin and skeletal abnormalities, growth defects

Werner syndrome
(WS)

WRN
(bi-allelic mutations)

Cancer:
Sarcomas
Progeria:
Atherosclerosis, cataracts, gray hair, osteoporosis
Other:
Type II diabetes, growth defects

Ataxia telangiectasia
(AT)

ATM
(bi-allelic mutations)

Cancer:
Lymphomas, leukemias
Neurological defects:
Ataxia, cerebellar degeneration, oculomotor apraxia
Immunodeficiency
Other:
Dilated blood vessel, infertility, metabolic defects, growth defects

Li e Fraumeni
syndrome (LFS)

p53
(heterozygous mutations)

Cancer:
Brain and breast cancer, sarcomas