《会读才会写》之如何阅读引言

一篇文章的引言为整个文章的逻辑前进设定了路线，以Jens G. Lohr等人于2014年在Cancer cell上发表的文章《Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy》的引言为例：

(1)We previously reported the sequencing of 38 matched tumor/normal MM pairs, and that report of the genomic landscape of MM pointed to a number of recurrently mutated genes (e.g. FAM46C, DIS3) that are likely causal drivers of the disease (Chapman et al., 2011). (2)However, that study design was only powered to detect commonly mutated genes, but not less commonly mutated genes, due to the weak statistical power provided by the small sample size. (3)It also did not examine copy number alterations, leading to homozygous deletions or loss of heterozygosity (LOH), or clonal heterogeneity due to the modest sequence coverage (~ 30X) of those whole genome sequences.

（1）The identification of driver mutations in MM holds great promise for personalized medicine, whereby patients with particular mutations would be treated with the appropriate targeted therapy (Fonseca et al., 2009; Mahindra et al., 2012; Palumbo and Anderson, 2011). （2）However, if the mutation is present in only a fraction of the cells, one might doubt whether such targeted therapy would be clinically efficacious. （3）Recent studies have documented the existence of clonal heterogeneity in solid tumors and acute myeloid leukemia, albeit in small numbers of patients (Campbell et al., 2010; Carter et al., 2012; Ding et al., 2012; Gerlinger et al., 2012; Nik-Zainal et al., 2012; Shah et al., 2012; Walter et al., 2012). （4）These studies demonstrated how acquisition of genetic alterations over time leads to clonal evolution. （5）Systemic treatment with chemotherapy may affect the fitness of some subclones more than others, and thus may alter the tumor composition by promoting particular subclones (Landau et al., 2013b). （6）Consequently, the full breadth of tumor heterogeneity, particularly in solid malignancies, may not be captured in a single biopsy, which represents a challenge for cancer therapy (Gerlinger et al., 2012). （7）Clonal heterogeneity and clonal evolution have also been observed in MM by either whole exome sequencing or array CGH, albeit in a modest number of patients (Egan et al., 2012; Keats et al., 2012; Walker et al., 2012).

We therefore sought to estimate the extent of clonal heterogeneity in MM in a large-scale MM genome sequencing dataset capturing a breadth of untreated and previously treated patients, and to infer the timing of genetic events in MM. In the work presented here, we address several important questions: 1) Can we identify significantly mutated genes by integrating evidence from both point mutations and copy number analysis? 2) How do the mutation profile and the clonal and subclonal composition of MM differ between hyperdiploid and non-hyperdiploid and between treated and untreated MM? 3) Can the contribution of subclones in a patient be reconstructed from a single biopsy to inform targeted therapy?

整个引言分为三段：

• 第一段第（1）句是是对现有的研究作综述，因此在这句右侧标注SPL(Summary of Previous Literatures)

• 第一段第（2）（3）句对现有研究进行了批评，给出了研究空白，因此在右侧标注CPL/GAP（Critique of Previous Literature/Gaps of Previous Literature）

• 第二段的内容依然为SPL，不过最后几句同时也点出了本研究的重要理由（RAT, Rational），即携带不同亚克隆病人的系统性治疗的肿瘤适应性是不同的，并且克隆的异质性是在很多病人中都观察到的。

• 第三段给出了本文的做法，在右侧标注WTD(What They Do)

这4段采用的招式是SPL => CPL => GAP => RAT => WTD。了解了这些基本元素后，在阅读文献的时候就可以更清楚地看出文章的展开逻辑是怎样的。有时候作者的断言并没有在引言里面详细地展开，导致了明显的漏洞（MOP，Missed Obvious Point）.