A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer.
A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer.
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DOI：
10.1038/s41467-018-05226-0
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发表时间：
2018-07-23
影响因子：
16.6
通讯作者：
Mimori K
中科院分区：
文献类型：
--
作者：
Saito T;Niida A;Uchi R;Hirata H;Komatsu H;Sakimura S;Hayashi S;Nambara S;Kuroda Y;Ito S;Eguchi H;Masuda T;Sugimachi K;Tobo T;Nishida H;Daa T;Chiba K;Shiraishi Y;Yoshizato T;Kodama M;Okimoto T;Mizukami K;Ogawa R;Okamoto K;Shuto M;Fukuda K;Matsui Y;Shimamura T;Hasegawa T;Doki Y;Nagayama S;Yamada K;Kato M;Shibata T;Mori M;Aburatani H;Murakami K;Suzuki Y;Ogawa S;Miyano S;Mimori K
晚期结直肠癌具有广泛的中性演变形成的瘤内异质性，然而，结直肠癌前病变的瘤内异质性研究很少。我们对10例早期结直肠肿瘤进行了多区域全外显子组测序，其中包括腺瘤和原位癌。通过与晚期结直肠肿瘤的测序数据进行比较，我们发现早期肿瘤比晚期肿瘤积累了更高比例的亚克隆驱动突变，KRAS和APC的亚克隆突变突出了这一点。我们还表明，亚克隆突变的变异等位基因频率往往在早期肿瘤较高，这表明亚克隆突变在早期肿瘤发生中受到选择性扫描，而中性进化在晚期占主导地位。这项研究表明，在结直肠肿瘤进展过程中，肿瘤内异质性的进化原理从达尔文进化论转变为中性进化论。晚期结直肠癌的特征在于由中性演变决定的肿瘤内异质性。在这里，作者通过全外显子组测序分析了早期结直肠肿瘤，发现达尔文进化决定了结直肠腺瘤和原位癌早期病变的命运。
Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression. Advanced colorectal cancers are characterised by intra-tumour heterogeneity dictated by neutral evolution. Here the authors analyse early colorectal tumours by whole-exome sequencing and find that Darwinian evolution determines the fate of early lesions in colorectal adenoma and carcinoma in situ.
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DOI：
10.1093/annonc/mdu479
发表时间：
2015-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Favero F;Joshi T;Marquard AM;Birkbak NJ;Krzystanek M;Li Q;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
影响因子：
30.8
作者：
Makohon-Moore AP;Zhang M;Reiter JG;Bozic I;Allen B;Kundu D;Chatterjee K;Wong F;Jiao Y;Kohutek ZA;Hong J;Attiyeh M;Javier B;Wood LD;Hruban RH;Nowak MA;Papadopoulos N;Kinzler KW;Vogelstein B;Iacobuzio-Donahue CA
通讯作者：
Iacobuzio-Donahue CA
影响因子：
17.1
作者：
McGranahan N;Favero F;de Bruin EC;Birkbak NJ;Szallasi Z;Swanton C
通讯作者：
Swanton C
影响因子：
4.7
作者：
Losi, L;Baisse, B;Benhattar, J
通讯作者：
Benhattar, J
影响因子：
24.5
作者：
Carvalho, B.;Postma, C.;Meijer, G. A.
通讯作者：
Meijer, G. A.