Rare variant (Glu to Lys) in the leucine zipper region of CHOP (GADD153).
CHOP (GADD153) has been shown to be a dominant negative inhibitor of specific transcription factors. Direct sequencing of the gene, amplified from the DNA of a Li-Fraumeni family index case (liposarcoma, breast cancer) revealed a constitutional variant within the coding region. This alteration, though not responsible for the Li-Fraumeni phenotype, resulted in a glutamic acid to lysine switch within the leucine zipper domain, at a residue conserved between CHOP and its potential target molecules and between the human and hamster sequences. The variant created a Taq I restriction fragment length polymorphism (RFLP) facilitating screening. Analysis of 159 breast tumour DNA samples detected two encoding variant alleles (tumour and constitutional DNA).
Heighway
J
J
CRC Dept of Cancer Genetics, Paterson Institute for Cancer Research, Christie CRC Research Centre, Manchester, UK.
White
G R
GR
Hartley
A L
AL
Birch
J M
JM
Santibánez-Koref
M F
MF
D000328:Adult; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000037:antagonists & inhibitors*
D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051742:Transcription Factor CHOP