Many colorectal cancers are "flat" clonal expansions.
Many colorectal cancers are "flat" clonal expansions.
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DOI：
10.4161/cc.8.14.9151
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Shibata D
中科院分区：
文献类型：
--
作者：
Siegmund KD;Marjoram P;Tavaré S;Shibata D
群体遗传学家可以根据当今个体的多态性重建宏观群体的祖先。例如，“走出非洲”的迁徙就记录在世界不同地区的人类基因组变异中。在这里，我们将这种方法应用于人类结直肠癌细胞群和多态性乘客甲基化模式。通过对同一癌症不同部位的分子变异进行采样，应该可以推断出单个肿瘤的生长方式，因为最近的克隆扩张应该比旧的扩张具有更少的多样性。癌症之间的平均多样性不同，这意味着某些癌症是比其他癌症更古老的克隆扩张。对于个体癌症，甲基化模式多样性在整个肿瘤中相对均匀（右侧与左侧、浅表性与侵袭性），这与单一、均匀或“平坦”克隆扩张比逐步顺序进展更一致。许多结直肠癌似乎在早期就侵袭和扩张，但随后停滞不前。单个小癌腺片段内的表观等位基因多样性很高，并且与常见而不是极其罕见的癌症干细胞（CSC）更加一致。这些研究表明，许多人类结直肠癌是相对古老的统一克隆扩张，癌细胞群包含频繁的长寿CSC谱系，并且一些过客甲基化模式记录了体细胞祖先。
Population geneticists can reconstruct the ancestries of macroscopic populations from polymorphisms in present day individuals. For example, the migration “out of Africa” is recorded in human genome variation in different parts of the world. Here we apply this approach to human colorectal cancer cell populations and polymorphic passenger methylation patterns. By sampling molecular variation from different parts of the same cancer, it should be possible to infer how individual tumors grow because recent clonal expansions should be less diverse than older expansions. Average diversity was different between cancers implying that some cancers are older clonal expansions than others. For individual cancers, methylation pattern diversity was relatively uniform throughout the tumor (right versus left side, superficial versus invasive), which is more consistent with a single, uniform or “flat” clonal expansion than with stepwise sequential progression. Many colorectal cancers appear to invade and expand early, but subsequently stall. Epiallele diversity within individual small cancer gland fragments was high and more consistent with frequent rather than extremely rare cancer stem cells (CSCs). These studies suggest that many human colorectal cancers are relatively old uniform clonal expansions, that cancer cell populations contain frequent long-lived CSC lineages, and that some passenger methylation patterns record somatic cell ancestry.
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影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
DOI：
10.1073/pnas.0712345105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Jones, Sian;Chen, Wei-dong;Markowitz, Sanford D.
通讯作者：
Markowitz, Sanford D.
DOI：
10.1073/pnas.0810276106
发表时间：
2009-03-24
影响因子：
11.1
作者：
Siegmund, Kimberly D.;Marjoram, Paul;Shibata, Darryl
通讯作者：
Shibata, Darryl
影响因子：
14.9
作者：
CLARK, SJ;HARRISON, J;FROMMER, M
通讯作者：
FROMMER, M
影响因子：
4.3
作者：
Shibata, D;Tavaré, S
通讯作者：
Tavaré, S