Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Abstract

Summary Molecular and immunohistochemical studies of genetic events on chromosome 17p were prospectively compared with conventional clinical and pathological parameters and disease behaviour at a minimum of 72 months follow-up. In a series of 91 patients with primary operable breast cancer, 37 out of 91 (41 %) patients had disease relapse and 23 out of 91 (25%) had died during the follow-up period. Allelic imbalance at the YNZ22 locus (1 7p1 3.3), demonstrated in 33 out of 63 (52%) informative patients, was significantly associated with disease recurrence (P < 0.01, 2 d.f. Cox analysis) and showed a trend towards impaired survival (P = 0.08, 2 d.f. Cox analysis) after a mean follow-up of 84 months for survivors. By contrast, p53 mutation (in 10 out of 60, 17% of cancers), p53 allelic imbalance (in 23 out of 56, 41% informative patients), p53 mRNA expression (in 47 out of 87, 54% patients), p53 mRNA overexpression (in 24 out of 87, 28%) or p53 protein expression (detected in 25/76, 32%) were not associated with disease behaviour. There was no significant association between allelic imbalance at YNZ22 and any abnormality of p53 DNA, RNA or protein. Allelic imbalance at 17p13.3 (YNZ22) serves as a marker of poor prognosis in breast cancer. As yet unidentified genes on 17p13.3, distinct from and telomeric to p53, are therefore likely to be of clinical importance in breast cancer.

Physical Map of 17p13 and the Genes Adjacent to p53

“…Other genes mapping to 17p12-p13 potentially close to p53, such as retina-specific guanylate cyclase, have been examined, yet thus far no precise physical information on the chromosomal region is available. Studies on allele loss in breast cancer and medulloblastoma suggest the presence of another tumor suppressor gene telomeric to p53 (Thompson et al, 1998;Cornelis et al, 1994;McDonald et al, 1994). Although the hypothetical gene is predicted to be roughly 10 Mb telomeric to the p53 gene, the present map should provide useful landmarks.…”

An immunochemical analysis of mdm2 expression in human breast cancer and the identification of a growth-regulated cross-reacting species p170

“…These patients have been previously reported. 36,37 Tumour samples were handled identically and immediately snap frozen in liquid nitrogen prior to storage at 80 C until required. Frozen tissue samples were homogenized using plastic pellet mixers (Scotlab, Coatbridge) in approximately 100 l lysis buffer (1 per cent Igepal, 25 mM Hepes, 0·4 M KCl, 5 mM EDTA pH 8·0, 5 mM DTT, 5 mM PMSF, 10 mM NaF, Pepstatin 1 g/ml, 1 g/ml, 1 mM Benzamidine) per 1 mg sample.…”

Gain-of-Function Activity of Mutant p53 in Lung Cancer through Up-Regulation of Receptor Protein Tyrosine Kinase Axl

“…In general, tumors with p53 mutations have poor prognosis. [1][2][3][4][5][6] The majority of clinical studies suggest that lung cancers with p53 alterations carry a worse prognosis and may be relatively more resistant to chemotherapy and radiation. 7 More than 50% of the p53 mutations found in cancer are missense mutations, and in most human cancers, only the mutant protein is expressed.…”