Bogdanovic G, Pou C, Barrientos-Somarribas M, Bjerkner A, Honkaniemi E, Allander T, Andersson B, Gustafsson B
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Department of Clinical Microbiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Br J Cancer. 2016 Oct 11;115(8):1008-1014. doi: 10.1038/bjc.2016.261. Epub 2016 Aug 23.
Some childhood acute lymphoblastic leukaemias (ALL) can be traced back to a prenatal origin, where a virus infection could be involved in the first pre-leukaemic clone development. The DNA virome of 95 children who later developed ALL was characterised from neonatal blood spots (NBS) using unbiased next-generation sequencing (NGS) and compared with the virome of 95 non-ALL controls.
DNA was individually extracted from the ALL-patients and controls, pooled, randomly amplified and sequenced using the Illumina MiSeq Sequencing System.
Virus-like sequences identified in both groups mapped to human endogenous retroviruses and propionibacterium phage, considered a part of the normal microbial flora. Potential pathogens human herpesvirus type 6 (HHV-6) and parvovirus B19 were also identified, but only few samples in both ALL and controls tested positive by PCR follow-up.
Unbiased NGS was employed to search for DNA from potential infectious agents in neonatal samples of children who later developed ALL. Although several viral candidates were identified in the NBS samples, further investigation by PCR suggested that these viruses did not have a major role in ALL development.
一些儿童急性淋巴细胞白血病(ALL)可追溯到产前起源,其中病毒感染可能参与了首个白血病前期克隆的发展。利用无偏差下一代测序(NGS)技术,对95名后来患ALL的儿童的新生儿血斑(NBS)中的DNA病毒组进行了特征分析,并与95名非ALL对照儿童的病毒组进行了比较。
从ALL患者和对照中分别提取DNA,混合后使用Illumina MiSeq测序系统进行随机扩增和测序。
两组中鉴定出的病毒样序列与人类内源性逆转录病毒和丙酸杆菌噬菌体匹配,后者被认为是正常微生物群的一部分。还鉴定出了潜在病原体人类疱疹病毒6型(HHV-6)和细小病毒B19,但通过PCR后续检测,ALL组和对照组中均只有少数样本呈阳性。
采用无偏差NGS技术在后来患ALL的儿童的新生儿样本中寻找潜在感染因子的DNA。虽然在NBS样本中鉴定出了几种病毒候选物,但PCR进一步研究表明,这些病毒在ALL的发展中没有主要作用。