Z**********g
发帖数: 222 | 1 感觉很promising,可以解决不少争议问题:
1.CSC or clonal evolution:我觉得cancer genomics数据还是比较支持clonal
evolution模型的.从现有的ancer genomics数据来看,任何一个肿瘤里面可能存在成千
上万的突变,而且各个突变(包括点突变,拷贝数,重排等)的发生率迥异,表明随机突变和
克隆进化必然存在.这种genetic heterogeneity不太容易由CSC模型解释.毕竟CSC模型
从本质上来说更强调epigenetics.另外,把一个肿瘤里的CSC和nonCSC拿出来测序对比,
我觉得突变图谱肯定也不一样(虽然目前我还没有看到这方面的证据)
肿瘤本质上是基因病,根源是基因组不稳定性,所以我支持clonal evolution.
2.The relationship between primary and metastasis:对于转移,一个关键的问题是
早期还是晚期事件.如果转移发生在早期,原发瘤和转移瘤应该是平行进化,那么各自的
突变图谱应该比较divergent,而发生在晚期的话,应该convergence比较多.现在有好几
篇文章对同一病人的原发和转移瘤进行genomic sequencing了,这些数据似乎更支持转
移是晚期事件.
3.Cancer genomics也可以指导个体化治疗.
大家怎么看? | p******d
发帖数: 3737 | | c******r
发帖数: 3778 | | a*****g
发帖数: 543 | 4 Just my two cents:
1. 我不反对也不支持CSC的model.但是光从mutation的普遍性来说并不能否定CSC. 我
们现在还没法确定这些genetic heterogeneity是driver 还是passager.大多数只是ca
ncer的result而不是cause。Moreover, it is possible that CSC and Non-CSCs all
have genetic changes;remember the so-called CSCs don't have to follow the
biology of typical stem cells.
If cancer strictly follows evolution model, should one imagine certain gene
tic lesions gain dominance?
As for the genomic stability, why should we believe it is promoting tumor?
As far as I know, our normal cells do not like any abnormal genomes would c
ommit senescence or apoptosis once such things happen. Is there any thing h
appen （critical possibly) before we observe such global genetic mutations?
it is interesting to note Down syndrome patients (an extra chromosome, shou
ld reflect some genome instability) have fewer incidence to get cancer.
2. I'm assuming you are refering the two recent pancreatic cancer sequencin
g paper on Nature? both are excellent sequencing papers and hopefully will
followed up with other paper as well. However, i do doubt the metastasis is
that late. In mouse models, circulating tumor cells are detected early rat
her than late. In car accident autoposies, it is not rare to detect both pr
imary tumor and lung mets.
I guess when the sequencing tech improves to single-cell level these questi
ons should be fairly easy to address.
3. totally agree. It's like 对症下药...
【在 Z**********g 的大作中提到】
: 感觉很promising,可以解决不少争议问题:
: 1.CSC or clonal evolution:我觉得cancer genomics数据还是比较支持clonal
: evolution模型的.从现有的ancer genomics数据来看,任何一个肿瘤里面可能存在成千
: 上万的突变,而且各个突变(包括点突变,拷贝数,重排等)的发生率迥异,表明随机突变和
: 克隆进化必然存在.这种genetic heterogeneity不太容易由CSC模型解释.毕竟CSC模型
: 从本质上来说更强调epigenetics.另外,把一个肿瘤里的CSC和nonCSC拿出来测序对比,
: 我觉得突变图谱肯定也不一样(虽然目前我还没有看到这方面的证据)
: 肿瘤本质上是基因病,根源是基因组不稳定性,所以我支持clonal evolution.
: 2.The relationship between primary and metastasis:对于转移,一个关键的问题是
: 早期还是晚期事件.如果转移发生在早期,原发瘤和转移瘤应该是平行进化,那么各自的
| b****r
发帖数: 17995 | 5 有这功夫干嘛不去研究人群的进化和对疾病易感性？效益大多了，技术上更容易，因为
cancer你几乎拿不到均一的细胞，而且也许每个人的某个阶段的那一个cancer都是独特的
我认为cancer genetics目前还根本不到时候。人群基因组的分析将是下一个boost，而
且是会真正产生经济效益的boost | Z**********g
发帖数: 222 | 6 Insightful, but just argue some points:
1. "If cancer strictly follows evolution model, should one imagine certain
genetic lesions gain dominance?" 某些肿瘤可能的确是这样的,比如一些EGFR突变
的NSCLC,表现出oncogene addictive,这种genetic lesion似乎dominate肿瘤的生长,因
为对突变的EGFR进行target therapy（erlotinib）具有疗效．当然oncogene
addictive也并不排斥CSC.
2. 关于癌基因会诱导正常细胞senescence or apoptosis.这是事实，但一种可能的解
释是，这种或这些癌基因并非是tumor initiator,它们只是promoter或maintainer;也
就是说在它们异常之前，有其他genetic lesions作为tumor initiating factors，而
这些我们还没找到？
3.对Down syndrome了解不多，21 chromosome存在重要的抑癌基因？或者他们的寿命
比较短，没时间长肿瘤？
4.对于转移，circulating tumor cells are detected early rather than late是对
的，但也看到一篇paper，表明早期circulating tumor cells可以到达靶器官，但它们
不能colonization;而晚一些的circulating tumor cells最终形成转移灶。也许
circulating tumor cells伴随整个肿瘤发生发展的过程，但只有特定时期的
circulating tumor cells具备完全的转移能力。
Single-cell level sequencing would be fantastic.
ca
all
gene
【在 a*****g 的大作中提到】
: Just my two cents:
: 1. 我不反对也不支持CSC的model.但是光从mutation的普遍性来说并不能否定CSC. 我
: 们现在还没法确定这些genetic heterogeneity是driver 还是passager.大多数只是ca
: ncer的result而不是cause。Moreover, it is possible that CSC and Non-CSCs all
: have genetic changes;remember the so-called CSCs don't have to follow the
: biology of typical stem cells.
: If cancer strictly follows evolution model, should one imagine certain gene
: tic lesions gain dominance?
: As for the genomic stability, why should we believe it is promoting tumor?
: As far as I know, our normal cells do not like any abnormal genomes would c
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