Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence.
Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence.
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DOI：
10.1038/s41467-020-18730-z
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发表时间：
2020-10-06
影响因子：
16.6
通讯作者：
Alvarez JV
中科院分区：
文献类型：
--
作者：
Walens A;Lin J;Damrauer JS;McKinney B;Lupo R;Newcomb R;Fox DB;Mabe NW;Gresham J;Sheng Z;Sibley AB;De Buysscher T;Kelkar H;Mieczkowski PA;Owzar K;Alvarez JV
治疗后残留肿瘤细胞的存活和复发是乳腺癌治疗的最大障碍之一，但肿瘤的克隆性成分在复发过程中如何变化尚不清楚。我们使用细胞条形码来监测体内肿瘤复发期间的克隆动力学。我们发现在肿瘤消退、残留病变和复发过程中克隆多样性降低。休眠残存细胞的复发遵循几种不同的途径。大约一半的复发肿瘤表现出克隆性优势，少数亚克隆构成了肿瘤的绝大多数；这些克隆性复发通常依赖于Met基因的扩增。第二组复发肿瘤由数千个亚克隆组成，具有类似于原发肿瘤的克隆性结构，并依赖于JAK/STAT途径。因此，休眠肿瘤的再生通过多种途径进行，产生具有不同克隆成分、遗传改变和药物敏感性的复发肿瘤。复发肿瘤的细胞成分可以提供对治疗抵抗的洞察和二线治疗的信息。在这里，作者使用转基因小鼠对原发肿瘤进行条形码实验，以使他们能够研究肿瘤复发的克隆动力学。
The survival and recurrence of residual tumor cells following therapy constitutes one of the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how the clonal composition of tumors changes during relapse. We use cellular barcoding to monitor clonal dynamics during tumor recurrence in vivo. We find that clonal diversity decreases during tumor regression, residual disease, and recurrence. The recurrence of dormant residual cells follows several distinct routes. Approximately half of the recurrent tumors exhibit clonal dominance with a small number of subclones comprising the vast majority of the tumor; these clonal recurrences are frequently dependent upon Met gene amplification. A second group of recurrent tumors comprises thousands of subclones, has a clonal architecture similar to primary tumors, and is dependent upon the Jak/Stat pathway. Thus the regrowth of dormant tumors proceeds via multiple routes, producing recurrent tumors with distinct clonal composition, genetic alterations, and drug sensitivities. The cellular composition of recurrent tumors can provide insight into resistance to therapy and inform on second line therapies. Here, using a genetically modified mouse, the authors perform barcoding experiments of the primary tumors to allow them to study the clonal dynamics of tumor recurrence.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
82.9
作者：
Bivona TG;Doebele RC
通讯作者：
Doebele RC
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J