8q24 Copy number gains and expression of the c‐myc mRNA stabilizing protein CRD‐BP in primary breast carcinomas

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Abstract
The coding region determinant binding protein (CRD‐BP) was isolated by virtue of its high affinity to the c‐myc mRNA coding region stability determinant and shown to shield this message from nucleolytic attack, prolonging its half‐life. CRD‐BP is normally expressed during fetal life but is also activated de novo in tumors. Considering that aberrant CRD‐BP expression may represent an additional mechanism interfering with c‐myc regulation, we screened 118 primary breast carcinomas for CRD‐BP expression, 60 of which had also been analyzed by comparative genomic hybridization (CGH). Copy number gains encompassing 8q24, the chromosome band that contains the c‐myc locus, were detected in 48.3% (29/60) of tumors, whereas gains involving band 17q21, which contains the CRD‐BP locus, were observed in 18.3% (11/60) of tumors. CRD‐BP expression was detected in 58.5% (69/118) of tumors, implying mechanisms of activation alternative to gene amplification. Altogether, some 75% of the tumors had alterations pertaining to c‐myc since they either harbored 8q24 gains and/or expressed CRD‐BP. Significant associations were detected between CRD‐BP expression and the absence of estrogen receptors (p = 0.005) and between the presence of 8q24 gains and an increased number of genomic changes as measured by CGH (p = 0.0017). Tumors were divided into 4 groups according to CRD‐BP expression and 8q24 gains. The odds for tumors having both characteristics to be classified as poorly differentiated (grade III vs. grade I and II) were 19.6 times the corresponding odds for tumors neither expressing CRD‐BP nor harboring 8q24 gains. For tumors either harboring 8q24 gains only or expressing CRD‐BP alone, the corresponding odds were 6.4 and 3, respectively.