CHROMOSOME-I ALTERATIONS IN BREAST-CANCER - ALLELIC LOSS ON IP AND IQ IS RELATED TO LYMPHOGENIC METASTASES AND POOR PROGNOSIS
CHROMOSOME-I ALTERATIONS IN BREAST-CANCER - ALLELIC LOSS ON IP AND IQ IS RELATED TO LYMPHOGENIC METASTASES AND POOR PROGNOSIS
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DOI：
10.1002/gcc.2870050406
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发表时间：
1992-11-01
影响因子：
3.7
通讯作者：
WENNGREN, E
中科院分区：
文献类型：
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作者：
BORG, A;ZHANG, QX;WENNGREN, E
人类乳腺癌的发展以多种遗传改变为特征，细胞遗传学分析已经证明了1号染色体两臂的一致参与。在本研究中，检测限制性片段长度多态性的分子标记被用于成对筛选正常和肿瘤DNA，以确定乳腺肿瘤中等位基因失衡的频率。在89例信息性（组成性杂合）病例中，16%的病例发现1 q21多态性上皮粘蛋白（PEM或MUCI）基因杂合性缺失（洛），而一条等位基因条带强度增加更常见（37%），共有47%的病例表现为等位基因缺失或增加。另外三个肿瘤表现出结构改变。PEM基因的等位基因丢失或获得与其他预后因素无关，例如，肿瘤大小、淋巴结状态、类固醇受体、DNA倍性、S期分数、原癌基因扩增、组织学类型或患者年龄。然而，PEM基因的洛缺失与早期疾病复发显著相关（P = 0.006）。在117例有信息的病例中，27%的病例发现了1 p上的洛缺失，分别使用位于1 p33-p35和1 p36的D1 S57或D1 Z2探针。1 p和1 q上的体细胞等位基因不平衡似乎是独立的事件，而不是整个1号染色体丢失的影响。1 p位点的洛与淋巴结转移、较大肿瘤大小和DNA非二倍体显著相关，但在有限的随访时间（中位数29个月）内未发现与疾病结局相关。
The development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome 1. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA to determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin (PEM or MUCI) gene at 1q21 was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in the PEM gene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors, DNA ploidy, S phase fraction, protooncogene amplification, histological type, or patient age. However, LOH in the PEM gene was significantly correlated with early disease recurrence (P = 0.006). LOH on 1p was found in 27% of 117 informative cases, using probes for either D1S57 or D1Z2 located at 1p33-p35 and 1p36, respectively. Somatic allelic imbalance on 1p and 1q seemed to be independent events and not the effect of loss of a whole chromosome 1. LOH on 1p was significantly correlated to the presence of lymph node metastasis, to larger tumor size, and to DNA nondiploidy, but no correlation was found to disease outcome at this limited duration of follow-up (median 29 months).