Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours.
Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours.
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DOI：
10.1371/journal.pone.0028250
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tonin PN
中科院分区：
文献类型：
--
作者：
Birch AH;Arcand SL;Oros KK;Rahimi K;Watters AK;Provencher D;Greenwood CM;Mes-Masson AM;Tonin PN
卵巢癌表现出广泛的异质性，其病因仍不清楚。组织学和遗传学证据表明，低级别卵巢浆液性癌（LGOSC）与高级别癌（HGOSC）有不同的病因，由低恶性潜能浆液性肿瘤（LMP）引起。在所有类型的浆液性卵巢肿瘤中，包括良性肿瘤，都观察到了染色体（chr）3缺失的共同区域，这表明这些区域含有在所有卵巢浆液性癌的发展中重要的基因。一种高密度全基因组基因分型微珠阵列技术，分析了超过600，000个标记，应用于一组浆液性良性和LMP肿瘤和一小组LGOSC，以表征与最惰性形式的卵巢疾病相关的体细胞事件。推测的基因组模式与TP 53、KRAS和BRAF突变有关。随着疾病病理学的观察，基因组异常的频率增加：3/22（13.6%）良性病例，40/53（75.5%）LMP病例和10/11（90.9%）LGOSC病例。低频率的chr 3异常发生在所有类型的肿瘤。在chr 3上观察到的纯合性最多，其中3 p12-p11候选肿瘤抑制基因区是基因组中最常见的纯合区域。LMP在chr 6上具有纯合缺失，其产生GOPC-ROS 1融合基因，先前报道在其他癌症类型中为致癌基因。在良性肿瘤中未观察到体细胞TP 53、KRAS和BRAF突变。KRAS突变阳性的LMP病例比BRAF突变阳性或KRAS和BRAF突变阴性的病例显示出显著更多的染色体畸变。携带KRAS基因的12 p的增加特别明显。病理学审查重新分类了所有TP 53突变阳性的LGOSC病例，其中一些获得了HGOSC状态。综上所述，我们的研究结果支持LGOSC可能来自浆液性良性肿瘤和LMP肿瘤的观点，但不排除HGOSC可能来自LMP肿瘤的可能性。
Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
11.2
作者：
Charest, Al;Wilker, Erik W.;Housman, David
通讯作者：
Housman, David
影响因子：
4.6
作者：
Birch, Ashley H.;Quinn, Michael C. J.;Tonin, Patricia N.
通讯作者：
Tonin, Patricia N.
影响因子：
3.7
作者：
Gu TL;Deng X;Huang F;Tucker M;Crosby K;Rimkunas V;Wang Y;Deng G;Zhu L;Tan Z;Hu Y;Wu C;Nardone J;MacNeill J;Ren J;Reeves C;Innocenti G;Norris B;Yuan J;Yu J;Haack H;Shen B;Peng C;Li H;Zhou X;Liu X;Rush J;Comb MJ
通讯作者：
Comb MJ
影响因子：
8
作者：
Cody, N. A. L.;Ouellet, V.;Tonin, P. N.
通讯作者：
Tonin, P. N.