Laé Marick, La Rosa Philippe, Mandel Jonas, Reyal Fabien, Hupé Philippe, Terrier Philippe, Couturier Jérôme
Service de Pathologie, Institut Curie, PSL Research University, Paris, France.
Institut Curie, Paris, France.
J Clin Pathol. 2016 Dec;69(12):1081-1087. doi: 10.1136/jclinpath-2016-203684. Epub 2016 May 20.
The aim of this study was to analyse a series of borderline and malignant phyllodes tumours (PTs) of the breast by whole-genome profiling to identify genomic markers that could help to recognise potentially malignant tumours within borderline tumours.
We evaluated the genetic imbalances of a series of 53 PTs (30 borderline, 23 malignant) using the Human CNV370 BeadChip microarray (Illumina), containing 370 000 SNP markers and correlate this alterations with clinicopathological features.
Forty-five PTs (85%) showed chromosome copy number variations (CNVs). Twenty PTs (37%) showed five or more chromosomal imbalances (8/30 borderline (27%) and 12/23 malignant (52%)). The large-scale genetic changes associated with malignant were+7p (9/23), +1q (8/23), -10p (8/23), -13q14 (7/23), +8q (6/23) and +10q (6/23) and borderline were+1q (13/30), -13q14 (9/30), -6q (8/30) and -10p (8/30). Losses in 9p21.3, encompassing CDKN2A/B gene, were present in three tumours (malignant), whereas deletions of 13q, with a minimal region in 13q14.2 encompassing the RB1 gene, were found in 9/30 borderline and 7/28 malignant tumours. High-level amplifications were seen in eight tumours (seven malignant and one borderline): in 7p in three tumours (including EGFR in two), 7q31.2 (including TFEC and MET), 8q24.21 (including MYC) and 8q23.3 (including CSMD3) in one tumour each.
Whole-genome profiling by SNP arrays in PTs leads to identify a high number of CNV, gains of 7p and 8q, losses of 13q and 10, losses in 9p21.3 (CDKN2A/B) and the presence of amplifications, especially involving EGFR, as markers of potentially malignant tumours.
本研究旨在通过全基因组分析一系列乳腺交界性和恶性叶状肿瘤（PTs），以识别有助于在交界性肿瘤中识别潜在恶性肿瘤的基因组标志物。
我们使用包含370,000个单核苷酸多态性（SNP）标记的人类CNV370 BeadChip微阵列（Illumina）评估了53例PTs（30例交界性，23例恶性）的基因失衡情况，并将这些改变与临床病理特征相关联。
45例PTs（85%）显示出染色体拷贝数变异（CNVs）。20例PTs（37%）显示出五个或更多的染色体失衡（8/30例交界性（27%）和12/23例恶性（52%））。与恶性相关的大规模基因改变为+7p（9/23）、+1q（8/23）、-10p（8/23）、-13q14（7/23）、+8q（6/23）和+10q（6/23），与交界性相关的为+1q（13/30）、-13q14（9/30）、-6q（8/30）和-10p（8/30）。包含CDKN2A/B基因的9p21.3区域缺失出现在3例肿瘤（恶性）中，而13q缺失，其最小区域位于13q14.2包含RB1基因，在9/30例交界性肿瘤和7/28例恶性肿瘤中被发现。在8例肿瘤（7例恶性和1例交界性）中观察到高水平扩增：3例肿瘤中7p扩增（2例包括表皮生长因子受体（EGFR）），1例肿瘤中7q31.2扩增（包括TFEC和MET），1例肿瘤中8q24.21扩增（包括MYC），1例肿瘤中8q23.3扩增（包括CSMD3）。
通过SNP阵列对PTs进行全基因组分析可识别大量的CNV、7p和8q的增加、13q和10的缺失、9p21.3（CDKN2A/B）的缺失以及扩增的存在，尤其是涉及EGFR的扩增，作为潜在恶性肿瘤的标志物。
