Kuijper Arno, Snijders Antoine M, Berns Els M J J, Kuenen-Boumeester Vibeke, van der Wall Elsken, Albertson Donna G, van Diest Paul J
Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Cell Oncol. 2009;31(1):31-9. doi: 10.3233/clo-2009-0457.
Breast phyllodes tumour (PT) is a rare fibroepithelial tumour. The genetic alterations contributing to its tumorigenesis are largely unknown. To identify genomic regions involved in pathogenesis and progression of PTs we obtained genome-wide copy number profiles by array comparative genomic hybridization (CGH).DNA was isolated from fresh-frozen tissue samples. 11 PTs and 3 fibroadenomas, a frequently occurring fibroepithelial breast tumour, were analyzed. Arrays composed of 2464 genomic clones were used, providing a resolution of ~1.4 Mb across the genome. Each clone contains at least one STS for linkage to the human genome sequence.No copy number changes were detected in fibroadenomas. On the other hand, 10 of 11 PT (91%) showed DNA copy number alterations. The mean number of chromosomal events in PT was 5.5 (range 0-16) per case. A mean of 2.0 gains (range 0-10) and 3.0 losses (range 0-9) was seen per case of PT. Three cases showed amplifications. DNA copy number change was not related to PT grade. We observed recurrent loss on chromosome 1q, 4p, 10, 13q, 15q, 16, 17p, 19 and X. Recurrent copy number gain was seen on 1q, 2p, 3q, 7p, 8q, 16q, 20.In this study we used array CGH for genomic profiling of fibroepithelial breast tumours. Whereas most PT showed chromosomal instability, fibroadenomas lacked copy number changes. Some copy number aberrations had not previously been associated with PT. Several well-known cancer related genes, such as TP53 and members of the Cadherin, reside within the recurrent regions of copy number alteration. Since copy number change was found in all benign PT, genomic instability may be an early event in PT genesis.
乳腺叶状肿瘤（PT）是一种罕见的纤维上皮性肿瘤。其肿瘤发生过程中的基因改变在很大程度上尚不清楚。为了确定参与PT发病机制和进展的基因组区域，我们通过阵列比较基因组杂交（CGH）获得了全基因组拷贝数图谱。从新鲜冷冻的组织样本中分离DNA。分析了11例PT和3例纤维腺瘤（一种常见的乳腺纤维上皮性肿瘤）。使用由2464个基因组克隆组成的阵列，在全基因组范围内提供约1.4 Mb的分辨率。每个克隆包含至少一个用于与人类基因组序列连锁的序列标签位点（STS）。在纤维腺瘤中未检测到拷贝数变化。另一方面，11例PT中的10例（91%）显示出DNA拷贝数改变。PT中每个病例的染色体事件平均数为5.5（范围0 - 16）。PT每个病例平均有2.0次增益（范围0 - 10）和3.0次缺失（范围0 - 9）。3例显示有扩增。DNA拷贝数变化与PT分级无关。我们观察到1号染色体长臂、4号染色体短臂、10号、13号染色体长臂、15号染色体长臂、16号、17号染色体短臂、19号和X染色体存在反复缺失。在1号染色体长臂、2号染色体短臂、3号染色体长臂、7号染色体短臂、8号染色体长臂、16号染色体长臂、20号染色体上观察到反复的拷贝数增加。在本研究中，我们使用阵列CGH对乳腺纤维上皮性肿瘤进行基因组分析。大多数PT显示出染色体不稳定性，而纤维腺瘤缺乏拷贝数变化。一些拷贝数畸变以前未与PT相关联。几个著名的癌症相关基因，如TP53和钙黏蛋白家族成员，位于拷贝数改变的反复出现区域内。由于在所有良性PT中都发现了拷贝数变化，基因组不稳定性可能是PT发生的早期事件。
