NMYC amplification, (2p24) The proto-oncogene N-MYC (MYCN), located on the distal short arm of chromosome 2 (2p24), encodes the MYCN transcriptional regulator, expressed predominantly during the peripheral neural crest development, and has a role in cell growth control and proliferation. This gene is essential for stem cells proliferation, migration and homeostasis, and is expressed mainly in the […]
Loss of PTEN, del(10q23). 10q23/CEP10 The phosphatase and tensin homolog gene (PTEN) on chromosome 10q23.3 is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN
cMYC amplification (8q24) The c-MYC oncogene is located in 8q24 and in its locus (8q24.2-q24.3) amplifications can be found frequently in various types of human tumors (c-MYC amplifications have been described in breast, lung, ovary, cervical and prostate cancer). Two of the most significant genetic alterations detected in prostate cancer include 8q24 gain and loss
RREB1 amplification, (6p25) The protein encoded by this gene is a zinc finger transcription factor that binds to RAS-responsive elements (RREs) of gene promoters. Diseases associated with RREB1 include melanoma and substance-induced psychosis. RREB1 is thought to beinvolved in Raf/Ras-mediated cell differentiation, possibly by enhancing the expression of Calcitonin, besides being a repressor of angiotensinogen gene and regulate the transcriptional activity of other cancer-related genes. FISH
BRAF amplification, (7q34) BRAF gene is involved in the MAPK signalling cascade (RAS-RAF-MEK-ERK) and in carcinogenesis development (malignant transformation of the BRAF kinase). Melanoma with activating BRAF V600E mutation has a high probability of having an increase in the number of copies of BRAF locus. An increase in the number of copies of BRAF locus can be
BRAF V600 mutation The V600E mutation in the BRAF gene, which is located on the long arm of chromosome 7, replaces at residue 600, a valine molecule for a glutamic acid molecule, V600E (1799 G> A). The resulting protein from this genetic alteration has 10 times more activity than the same protein in normal conditions.
Loss of P16, del(9p21) Interstitial deletions of the chromosome 9p21 segment encoding the p16/CDKN2A tumor suppressor gene are frequently observed in a variety of human cancers. The loss of the 9p21 locus, del(9p21), is an early and widespread chromosomal abnormality in patients with Barrett’s esophagus predisposed to esophageal adenocarcinoma. Recent studies suggest that endogenous P16
KRAS mutations RAS genes (H-RAS, K-RAS and N-RAS) code similar G proteins involved in growth and differentiation signals from the receptors tyrosine kinase to the core cells. The K-RAS gene is located on the short arm of chromosome 12 (12p12.1) and at a molecular level, there have been cases of colorectal cancer associated with mutations
Loss of LPL, del(8p22) Lipoprotein lipase (LPL) gene located at 8p22 region and c-myc gene located at the 8q24 region, allows for prognosis in prostate cancer. Two of the most significant genetic alterations detected in prostate cancer include 8q24 gain and loss 8p21-22 heterozygous. It has been found that deletion of LPL locus is observed in 68% of analyzed prostate cancers by FISH analysis.
HER-2/ERBB2 amplification (17q11.2-12) HER-2/neu gene, also known as ERBB2 or HER2, encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases, which plays a role in cell growth and is amplified and overexpressed in 20–30% of cases of primary human breast. Besides breat cancer, HER2 is also overexpressed/amplified in a
