Phelan C M, Borg A, Cuny M, Crichton D N, Baldersson T, Andersen T I, Caligo M A, Lidereau R, Lindblom A, Seitz S, Kelsell D, Hamann U, Rio P, Thorlacius S, Papp J, Olah E, Ponder B, Bignon Y J, Scherneck S, Barkardottir R, Borresen-Dale A L, Eyfjörd J, Theillet C, Thompson A M, Larsson C
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Cancer Res. 1998 Mar 1;58(5):1004-12.
The pattern of loss of heterozygosity (LOH) on chromosome 17 in human breast cancer is complicated and shows many different regions of loss. In an attempt to narrow down the relevant regions of LOH on chromosome 17, we have studied the deletion pattern and its association with clinical parameters in 1280 breast carcinoma-venous blood lymphocyte pairs. In total, 42 different chromosome 17 loci were investigated, and between 25 and 625 cases were analyzed at each locus. The frequency of LOH observed on the p arm was much higher than that observed on the q arm. The opposite effect was observed in 52 ovarian cancer cases investigated, with less LOH on 17p than on 17q. Patterns of loss consistent with interstitial and terminal deletions, as well as loss of either the p or q arm or monosomy 17 were observed. To determine whether loss at particular loci may be associated with biological features of breast tumors, clinical data including age of onset, family history of breast cancer, tumor histopathology, tumor size, estrogen receptor (ER) status, and occurrence of lymph node or distant metastases were collected for each case. Overall, large-sized, ER-negative, lymph node-positive ductal tumors showed the highest frequencies of LOH, with ER-negative and ductal tumors showing LOH for markers along the majority of the chromosome. Eight regions of chromosome 17 appear to be associated with human breast cancer, two on 17p and six on 17q. These regions were not necessarily in the areas exhibiting the highest frequencies of LOH but were defined by interstitial and terminal deletions in multiple independent cases. Seven of these regions showed statistically significant differences in LOH associated with clinical parameters. These data strongly suggest that loci on chromosome 17 may determine aspects of tumor presentation and disease behavior in human breast cancer and pinpoint candidate tumor suppressor gene loci.
人类乳腺癌中17号染色体上杂合性缺失（LOH）的模式很复杂，呈现出许多不同的缺失区域。为了缩小17号染色体上LOH的相关区域范围，我们研究了1280对乳腺癌 - 静脉血淋巴细胞中的缺失模式及其与临床参数的关联。总共研究了42个不同的17号染色体位点，每个位点分析了25至625例病例。在p臂上观察到的LOH频率远高于在q臂上观察到的频率。在研究的52例卵巢癌病例中观察到相反的效果，17p上的LOH比17q上的少。观察到与间质和末端缺失一致的缺失模式，以及p或q臂的缺失或17号染色体单体性。为了确定特定位点的缺失是否可能与乳腺肿瘤的生物学特征相关，收集了每个病例的临床数据，包括发病年龄、乳腺癌家族史、肿瘤组织病理学、肿瘤大小、雌激素受体（ER）状态以及淋巴结或远处转移的发生情况。总体而言，大型、ER阴性、淋巴结阳性的导管肿瘤显示出最高的LOH频率，ER阴性和导管肿瘤在染色体大部分区域的标记物上显示出LOH。17号染色体的八个区域似乎与人类乳腺癌相关，两个在17p上，六个在17q上。这些区域不一定在显示最高LOH频率的区域，但由多个独立病例中的间质和末端缺失定义。其中七个区域在与临床参数相关的LOH方面显示出统计学上的显著差异。这些数据强烈表明，17号染色体上的位点可能决定人类乳腺癌中肿瘤表现和疾病行为的某些方面，并确定候选肿瘤抑制基因位点。
