HIGH CELL-KINETICS IS ASSOCIATED WITH AMPLIFICATION OF THE INT-2, BCL-1, MYC AND ERBB-2 PROTOONCOGENES AND LOSS OF HETEROZYGOSITY AT THE DF3 LOCUS IN PRIMARY BREAST CANCERS
HIGH CELL-KINETICS IS ASSOCIATED WITH AMPLIFICATION OF THE INT-2, BCL-1, MYC AND ERBB-2 PROTOONCOGENES AND LOSS OF HETEROZYGOSITY AT THE DF3 LOCUS IN PRIMARY BREAST CANCERS
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DOI：
10.1002/ijc.2910610102
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发表时间：
1995-03-29
影响因子：
6.4
通讯作者：
MARIANICOSTANTINI, R
中科院分区：
文献类型：
--
作者：
CONTEGIACOMO, A;PIZZI, C;MARIANICOSTANTINI, R
细胞动力学是乳腺癌侵袭性的预测参数，在乳腺肿瘤发生过程中发生的突变可能有利于不受控制的细胞增殖。本研究分析了54例原发性乳腺癌中int-2、bcl-1、c-myc、c-erbB-2和DF3基因座的细胞动力学、临床病理特征和遗传改变，并进行了相关性分析。还研究了多位点突变的发生情况。通过胸腺嘧啶标记指数（TLI）测定肿瘤增殖活性。在11.2%的肿瘤中观察到int-2扩增（AMP）， bcl-1扩增（9.4%），c-myc扩增（5.7%），c-erbB-2扩增（8.6%）。在13.9%的肿瘤中检测到DF3位点杂合性缺失（LOH）。遗传改变显示与患者年龄和高TLI值有显著关联。AMP和LOH + AMP似乎与组织型、组织学分级、肿瘤大小或淋巴结状态没有统计学相关性。单独来看，DF-3基因座的等位基因缺失与所研究的任何临床病理特征均无显著相关性。在11.1%的肿瘤中检测到一个以上位点的改变，包括int-2/bcl-1、int-2/c-myc、int-2/bcl-1/c-erbB-2和c-myc/DF3。多重突变仅在分化程度较低的肿瘤中发现，包括该系列中最年轻患者的2例。(C) 1995 Wiley-Liss, Inc。
Cell kinetics is a predictive parameter of breast-cancer aggressiveness, and mutations occurring in mammary tumorigenesis may favor uncontrolled cell proliferation. In this study, cell kinetics, clinico-pathological characteristics and genetic alterations at the int-2, bcl-1, c-myc, c-erbB-2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at move than one locus was also studied. Tumor-proliferative activity was evaluated by determination of the thymidine labeling index (TLI). Amplification (AMP) of int-2 was observed in 11.2%, of bcl-1 in 9.4%, of c-myc in 5.7% and of c-erbB-2 in 8.6% of the carcinomas. Loss of heterozygosity (LOH) at the DF3 locus was detected in 13.9% of the tumors. Genetic alterations demonstrated a significant association with patient's age and high TLI values. AMP and LOH + AMP did not appear to be statistically related to histotype, histological grade, tumor size or lymph-node status. Alone, allele loss at the DF-3 locus was not significantly associated with any of the clinico-pathological characteristics studied. Alterations at more than one locus, including int-2/bcl-1, int-2/c-myc, int-2/bcl-1/c-erbB-2, and c-myc/DF3, were detected in 11.1% of the tumors. Multiple mutations were found only in less differentiated tumors, which included the 2 cases from the youngest patients of the series. (C) 1995 Wiley-Liss, Inc.