Cyclin D1, EMS1 and 11q13 Amplification in Breast Cancer

Abstract

Chromosome locus 11q13 is frequently amplified in a number of human cancers including carcinoma of the breast where up to 15% carry this chromosomal abnormality. Originally 11q13 amplification was thought to involve a single amplicon spanning many megabases, but more recent data have identified four core regions within 11q13 that can be amplified independently or together in different combinations. Although the region harbors several genes with known or suspected oncogenic potential, the complex structure of the amplicons and the fact that 11q13 is gene-rich have made definitive identification of specific genes that contribute to the genesis and progression of breast cancer a difficult and continuing process. To date CCND1, encoding the cell cycle regulatory gene cyclin D1, and EMS1, encoding the filamentous actin binding protein and c-Src substrate cortactin, are the favored candidates responsible for the emergence of two of the four amplification cores.

FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma

“…The 11q13 locus is known to be a frequently amplified region in several human cancers except HCC. 13 Thus, we hypothesized that the amplification of 11q13 may be involved in a marked response to sorafenib.…”

“…FGF3 and FGF4 genes are located side-by-side and are also closely located to the FGF19 and CCND1 genes (within 0.2 Mb of the 11q13 region). 13 The 11q13 region is known as a gene-dense region, and gene amplification of this region is frequently observed in various solid cancers (including breast cancer, squamous cell carcinoma of the head and neck, esophageal cancer, and melanoma) at frequencies of 13%-60%. 13 On the other hand, the frequency of FGF3/FGF4 amplification in HCC remains 19 In the present study, two of the 82 (2.4%) HCC samples exhibited FGF3/FGF4 gene amplification in the HCC series.…”

“…13 The 11q13 region is known as a gene-dense region, and gene amplification of this region is frequently observed in various solid cancers (including breast cancer, squamous cell carcinoma of the head and neck, esophageal cancer, and melanoma) at frequencies of 13%-60%. 13 On the other hand, the frequency of FGF3/FGF4 amplification in HCC remains 19 In the present study, two of the 82 (2.4%) HCC samples exhibited FGF3/FGF4 gene amplification in the HCC series. If only 2%-3% of HCC patients harbor the FGF3/FGF4 amplification, its value as a biomarker seems to be limited in clinics because a frequency of 2%-3% is too low to stratify the patients for specific targeted therapy.…”

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

“…Mammary epithelial cell-specific overexpression of cyclin D1 leads to mammary carcinoma; whereas in cyclin D1-deficient mice, mammary gland development is arrested before lobuloalveolar development highlighting the importance of cyclin D1 in mam-mary gland development [47]. Cyclin D1 is encoded by the CCDN1 gene, which is located on chromosome 11q13-a region of the genome commonly amplified in numerous human carcinomas including about 15 % of breast cancers [48,49]. The human cyclin D1 gene has a common polymorphism in the alternatively spliced area resulting in cyclin D1a and D1b proteins that differ in their carboxyl terminus [50].…”

Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer

“…Chromosome 11 harbors a gene-rich region, 11q13, which is amplified in approximately 15% of primary human breast cancers (Karlseder et al, 1994;Ormandy et al, 2003). The high frequency implies that the region contains oncogenes that more or less contribute to positive selection for cell proliferation and survival.…”