1 Introduction
Gene involved | Cytoband | Breast cancer risk | Syndrome | Clinical features |
---|---|---|---|---|
BRCA1
| 17q21 | High | Hereditary breast cancer and ovarian syndrome | Breast cancer, ovarian cancer |
BRCA2
| 13q12.3 | High | Hereditary breast cancer and ovarian syndrome | Breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, melanoma |
TP53
| 17p13.1 | High | Li-Fraumeni syndrome | Breast cancer Sarcomas Brain tumors |
ATM
| 11q22.3 | Intermediate | Louis-Bar syndrome | Lymphoma, cerebellar ataxia, immune deficiency, glioma, medulloblastoma, breast cancer |
CDH1
| 16q22.1 | Intermediate | Familial diffuse gastric cancer syndrome | Gastric cancer, lobular breast cancer |
PTEN
| 10q23.31 | Intermediate | Cowden syndrome | Increased risk of neoplasms: breast cancer, thyroid cancer, endometrial carcinomas, hamartomatous polyps of the gastrointestinal tract |
Bannayan-Riley-Rivalcaba syndrome | Breast cancer, meningioma | |||
STK1
| 19p13.3 | Intermediate | Peutz-Jeghers syndrome | Melanocytic macules of the lips and others multiple gastrointestinal hamartomatous polyps increased risk of neoplasms; breast, testis, pancreas and cervix |
NBS1 | 8q21 | Intermediate | Nijmegen breakage syndrome | Microcephaly,growth retardation, immunodeficiency and a marked susceptibility to cancer |
Moderate risk of breast cancer | ||||
BRIP/FANCJ
| 17q22 | Intermediate | Fanconi anemia | Developmental anomalies affecting the skeleton (absent or abnormal thumbs and radii), kidneys, heart or any other major organ system |
PALB2/FANCN
| 16p12 | Intermediate | Aplastic anaemia, acute myeloid leukaemia and squamous cell carcinoma, breast cancer | |
FANCA
| 16q24.3 | Low | ||
FANCE
| 6p22-p21 | Low | ||
MSH2
| 2p22-p21 | Low | Lynch cancer family syndrome | Endometrial cancer, colorectal cancer, breast cancer, ovarian cancer, genitourinary cancer, sarcomas, glioblastomas and leukaemia (often multiple) |
MSH3
| 5q11-q12 | Low | ||
MSH6
| 2p16 | Low | ||
MLH1
| 3p21.3 | Low | ||
PMS1
| 2q31-q33 | Low | ||
PMS2
| 7p22 | Low |
1.1 The BRCA1 and BRCA2 genes
1.1.1 Discovery
1.1.2 Structure
1.1.3 Function
1.1.4 Mutations
1.1.5 Population specific occurrence
1.2 Pathology of BRCA1 related breast cancer
1.2.1 Histology
1.2.2 Immunophenotype
1.2.3 Genetic profile
Locus | Frequency | p-value | ||||
---|---|---|---|---|---|---|
BRCA1 | BRCA2 | Sporadic | BRCA1 vs sporadic | BRCA2 vs sporadic | BRCA1 vs BRCA2 | |
Gains | ||||||
1cen-p13 | 89 | 68 | 87 | 0.054 | ||
3pter-p22 | 33 | 16 | 0 | 0.006 | ||
3q13-q27 | 67 | 56 | 13 | 0.000 | 0.073 | |
8p12-cent | 11 | 16 | 47 | 0.012 | ||
9p | 33 | 16 | 3 | 0.078 | ||
9q22-q34 | 0 | 32 | 3 | 0.013 | ||
10pter-p12 | 50 | 20 | 7 | 0.000 | ||
10p12-q21 | 36 | 4 | 3 | 0.089 | ||
13q3 | 25 | 8 | 0 | 0.059 | ||
16p | 17 | 24 | 57 | 0.019 | ||
18p | 28 | 16 | 3 | 0.025 | ||
Losses | ||||||
5cent-q23 | 72 | 40 | 27 | 0.025 | ||
14q1-q2 | 39 | 8 | 10 | 0.048 |
1.2.4 Prognosis
1.3 Pathology of BRCA2 related breast cancer
1.3.1 Histology
1.3.2 Immunophenotype
1.3.3 Genetic profile
1.3.4 Prognosis
1.4 Other hereditary breast cancer genes
1.4.1 TP53
Locus | Frequency | p-value | ||||
---|---|---|---|---|---|---|
BRCA1 | BRCA2 | Sporadic | BRCA1 vs sporadic | BRCA2 vs sporadic | BRCA1 vs BRCA2 | |
Gains | ||||||
1cen-p13 | 89 | 68 | 87 | 0.054 | ||
3pter-p22 | 33 | 16 | 0 | 0.006 | ||
3q13-q27 | 67 | 56 | 13 | 0.000 | 0.073 | |
8p12-cent | 11 | 16 | 47 | 0.012 | ||
9p | 33 | 16 | 3 | 0.078 | ||
9q22-q34 | 0 | 32 | 3 | 0.013 | ||
10pter-p12 | 50 | 20 | 7 | 0.000 | ||
10p12-q21 | 36 | 4 | 3 | 0.089 | ||
13q3 | 25 | 8 | 0 | 0.059 | ||
16p | 17 | 24 | 57 | 0.019 | ||
18p | 28 | 16 | 3 | 0.025 | ||
Losses | ||||||
5cent-q23 | 72 | 40 | 27 | 0.025 | ||
14q1-q2 | 39 | 8 | 10 | 0.048 |