全基因组测序技术可鉴别与癌症相关的基因突变

  近日，一篇发表于国际杂志EbioMedicine上的研究报告中，来自美国德州大学西南医学中心（UT Southwestern Medical Center）的研究人员指出，利用全基因组测序技术可以帮助鉴别病人患遗传性癌症的风险，这或许有助于开发出癌症预防及诊断的新型策略。

  本研究首次利用全基因组测序技术对258名癌症患者机体的基因组进行了分析，从而为改善诊断诱发癌症的突变的能力提供了一定帮助。研究者Theodora Ross教授说道，全基因组测序是一种新型的遗传工具，其可以更为精确地确定一个人机体DNA序列的信息，我们的研究结果显示，大约90%的临床鉴别突变都可以被检测出来，而且额外的癌症基因突变也可以被发现；这些遗传突变的发现并就可以有效帮助研究人员开发改善癌症患者护理及治疗的方法，也有助于发现一些新的癌症基因。

  所有癌症中大约5%至10%的癌症都是由于遗传性基因的突变而致，这些突变往往会代代相传，而BRCA1和BRCA2基因的突变就是引发遗传性乳腺癌的常见原因；而BRCA基因突变被认为是乳腺癌风险中最出名的致癌因子，但是其常常也会引发卵巢、前列腺及其它组织的癌症。另外许多不同的基因，比如ATM、CDH1、CHEK2等基因也和乳腺癌发病风险增加直接相关，而研究人员也在努力研究寻找其它影响癌症倾向的基因。

  本文研究中，研究人员开发了新技术来分析全基因组测序产生的大量数据，研究人员对比了携带BRCA1或BRCA2突变病人同未携带BRCA基因的病人的测序数据，结果显示在BRCA病人群体中都可以检测出BRCA1和BRCA2的基因突变。本文的研究结果指出，全基因组测序技术可以检测出非BRCA病人机体中的新型癌症基因突变，而后期还需要更为深入的探究来解释这些引发癌症的新型基因突变。

  最后研究者Ross指出，测序技术可以帮助我们在某些神秘的病人机体中发现新型的候选癌症基因突变，以便我们可以及时开发出应对这些新型突变的策略，从而帮助改善癌症患者的生活质量及身体健康。（转化医学网360zhyx.com）

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Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic
EBioMedicine doi:10.1016/j.ebiom.2014.12.003
Samantha B. Foleya, 1, Jonathan J. Riosb, c, 1, Victoria E. Mgbemenaa, Linda S. Robinsond, Heather L. Hampele, Amanda E. Tolande, Leslie Durhama, b, Theodora S. Rossa, d
Despite the potential of whole-genome sequencing (WGS) to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176) and those without (n = 82). Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500) in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS). Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF) variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks.