Gentile M, Olsen K, Dufmats M, Wingren S
Department of Biomedicine and Surgery, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
Br J Cancer. 1999 May;80(5-6):843-9. doi: 10.1038/sj.bjc.6690430.
Previous studies have demonstrated that the pathological features of breast cancer are more aggressive in younger women than in their older counterparts, and that young age may be an independent marker for adverse prognosis. These findings have raised the question whether these differences are also present at the molecular level. In order to characterize the genetic alterations associated with early-onset breast cancer, 102 cases selected for age under 37 at diagnosis were examined for loss of heterozygosity (LOH) at nine different loci on chromosomes 11, 13 and 17. Ninety cases (88%), exhibited LOH for at least one marker. The D17S855 marker, intragenic in the BRCA1 gene, showed a high proportion of LOH (63%), whereas the intragenic marker for the TP53 gene, HP53, exhibited LOH in 43% of the cases. On chromosome 11, frequencies of LOH peaked at the D11S969 and D11S387 markers, which expressed LOH in 53% and 48% of the informative cases, whereas D11S1818, which is proximate to the ATM gene, exhibited an LOH frequency of 24%. A statistically significant correlation was found between LOH at the D11S387 marker and poor survival (P = 0.028). No such correlation was found for the adjacent D11S969 marker, located approximately 500 kb centromeric to D11S387. We conclude that one or more as yet unidentified genes, situated in chromosome bands 11q24.1-q25, could be involved in the initiation and/or progression of breast cancer in younger women.
以往的研究表明，与老年女性相比，年轻女性乳腺癌的病理特征更具侵袭性，且年轻可能是不良预后的独立标志物。这些发现引发了一个问题，即这些差异在分子水平上是否也存在。为了表征与早发性乳腺癌相关的基因改变，对102例诊断时年龄在37岁以下的病例进行了研究，检测了11号、13号和17号染色体上9个不同位点的杂合性缺失（LOH）情况。90例（88%）至少有一个标记显示杂合性缺失。位于BRCA1基因内的D17S855标记显示出较高比例的杂合性缺失（63%），而TP53基因的基因内标记HP53在43%的病例中表现出杂合性缺失。在11号染色体上，D11S969和D11S387标记的杂合性缺失频率最高，在有信息的病例中分别为53%和48%表现出杂合性缺失，而靠近ATM基因的D11S1818标记的杂合性缺失频率为24%。发现D11S387标记的杂合性缺失与不良生存之间存在统计学显著相关性（P = 0.028）。与位于D11S387着丝粒侧约500 kb处的相邻D11S969标记未发现这种相关性。我们得出结论，位于11q24.1 - q25染色体带中的一个或多个尚未鉴定的基因可能参与了年轻女性乳腺癌的发生和/或发展。
