Classification

 secretory breast carcinoma

Susceptibility

 BRCA1
 BRCA2

Molecular biology

 allelotypes
 expression profiling
 proteomics: #11721633#

 comparative genomic hybridization

CGH revealed approximately 20 regions of recurrent increased DNA sequence copy number in breast tumors. These regions are predicted to encode dominantly acting genes that may play a role in tumor progression or response to therapy.

• AMplified regions

Three of these regions had been associated with established oncogenes

• ERBB2 (MIM.164870) at 17q12
• MYC (MIM.190080) at 8q24
• CCND1 (MIM.168461) and EMS1 (MIM.164765) at 11q13

In breast cancer, ERBB2, CCND1 and EMS1 amplification and overexpression are associated with decreased life expectancy, whereas MYC amplification has been associated with lymph node involvement, advanced stage, and an increased rate of relapse.

• 20q13: Amplification at 20q13 occurs in a variety of tumor types and is associated with aggressive tumor behavior. Kallioniemi et al. (1994) found increased copy number involving 20q13 in 40% of breast cancer cell lines and 18% of primary breast tumors.

  Regions	8q24	11q13	11q13	17q12	20q13
  Genes	MYC	CCDN1	EMS1	ERBB2	-

  Other comparative genomic hybridization studies revealed copy number gains at 20q13 in greater than 25% of cancers of the ovary, colon, head and neck, brain, and pancreas.

LOH

 1p
 4p
 5q
 8p12-p23
 11q
 14q
 16q
 17p
 17q

References

 Weigelt B, Peterse JL, van 't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005 Aug;5(8):591-602. PMID: #16056258#

 Hunter DJ, Riboli E, Haiman CA, Albanes D, et al.; National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A candidate gene approach to searching for low-penetrance breast and prostate cancer genes. Nat Rev Cancer. 2005 Dec;5(12):977-85. PMID: #16341085#

 Nathanson KL, Weber BL. "Other" breast cancer susceptibility genes: searching for more holy grail. Hum Mol Genet. 2001 Apr;10(7):715-20. PMID: #11257104#

 Welcsh PL, King MC. BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum Mol Genet. 2001 Apr;10(7):705-13. PMID: #11257103#

 Barcellos-Hoff MH. Three down and counting: the transformation of human mammary cells from normal to malignant in three steps. Trends Mol Med. 2001 Apr;7(4):142-3. PMID: #11286925#

 Stratton MR. Recent advances in understanding of genetic susceptibility to breast cancer. Hum Mol Genet. 1996;5 Spec No:1515-9. PMID: #8875258#