Full-length HLA sequencing in adult T cell leukemia-lymphoma uncovers multiple gene alterations.
Full-length HLA sequencing in adult T cell leukemia-lymphoma uncovers multiple gene alterations.
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DOI：
10.1038/s41375-021-01403-1
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发表时间：
2021-10
期刊：
影响因子：
11.4
通讯作者：
Masuzaki H
中科院分区：
文献类型：
--
作者：
Tamaki K;Morishima S;Suzuki S;Shigenari A;Nomura I;Yokota Y;Morichika K;Nishi Y;Nakachi S;Okamoto S;Fukushima T;Shiina T;Masuzaki H
成人T细胞白血病-淋巴瘤（ATL）是由人T细胞白血病病毒1型（HTLV-1）引起的外周T细胞淋巴系统恶性肿瘤。ATL的临床亚型与其预后密切相关，与惰性亚型（有利的慢性和阴燃）相比，侵袭性亚型（急性、淋巴瘤和不利的慢性）的预后极差[1]。人类白细胞抗原（HLA）在T细胞介导的癌细胞清除中起重要作用。HLA的下调发生在各种癌症中，并且与不良预后有关[2]。HLA分子的结构缺陷通常与HLA基因的杂合性缺失（洛）和体细胞突变有关[3]。然而，由于HLA基因的高度多态性，检测癌细胞中的洛缺失和体细胞突变似乎是极其困难的。传统的基于聚合酶链反应（PCR）的HLA分型主要集中在编码抗原识别结构域的多态性外显子。因此，在非编码区或多态性外显子外的外显子中的遗传变异在很大程度上仍然被忽视。此外，由于染色体相位模糊性，用于精确破译HLA等位基因的方法受到限制。为了克服一系列困难，我们成功开发了超高分辨率单分子序列分型（SS-SBT）方法[4]，该方法结合了远程PCR扩增和下一代测序（NGS）。该方法提供了同相高分辨率分型，包括HLA基因编码区和非编码区的核苷酸差异[5]。在这里，我们使用SS-SBT方法研究了从同一患者获得的ATL和非ATL细胞中的HLA基因的整个区域。我们评估了2012年至2018年期间诊断为ATL的25名患者。它们的特征总结在补充表1和2中。在所有患者中，5例为慢性型ATL，其余20例为急性型ATL。由于细胞粘附分子1（CADM 1）已知在ATL细胞中异位表达[6]，我们分离了外周血单核细胞（PBMC），
Adult T cell leukemia–lymphoma (ATL) is a peripheral T cell lymphoid malignancy caused by human T cell leukemia virus type 1 (HTLV-1). The clinical subtypes of ATL are closely associated with its prognosis, which is extremely poor in aggressive subtypes (acute, lymphoma, and unfavorable chronic) compared to indolent subtypes (favorable chronic and smoldering)[1]. Human leukocyte antigen (HLA) plays an important role in T cell-mediated elimination of cancer cells. Downregulation of HLA occurs in various cancers and has been linked to poor prognosis [2]. Structural defects in the HLA molecule are usually associated with loss of heterozygosity (LOH) and somatic mutations in HLA genes [3]. However, the detection of LOH and somatic mutations in cancer cells seems to be extremely difficult due to the highly polymorphic nature of HLA genes. Conventional polymerase chain reaction (PCR)-based HLA typing mainly focuses on the polymorphic exons encoding the antigen recognition domains. Therefore, the genetic variations in the non-coding regions or in the exons outside of the polymorphic exons have largely remained ignored. In addition, methods for precisely deciphering HLA alleles are limited due to chromosomal phase ambiguity. To overcome a line of difficulties, we successfully developed the super high-resolution singlemolecule sequence-based typing (SS-SBT) method [4], which combines long-range PCR amplification and next-generation sequencing (NGS). This method provides in phase highresolution typing, which includes nucleotide differences in both the coding and non-coding regions of HLA genes [5]. Here, we used the SS-SBT method to investigate the entire region of HLA genes in both ATL and non-ATL cells obtained from the same patients.We evaluated 25 patients diagnosed as ATL between 2012 and 2018. Their characteristics are summarized in Supplementary Tables 1 and 2. Of all the patients, five had chronic-type ATL; the remaining 20 had acute-type ATL. Because cell adhesion molecule 1 (CADM1) is known to be expressed ectopically in ATL cells [6], we separated peripheral blood mononuclear cells (PBMCs)
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影响因子：
7.3
作者：
Suzuki S;Ranade S;Osaki K;Ito S;Shigenari A;Ohnuki Y;Oka A;Masuya A;Harting J;Baybayan P;Kitazume M;Sunaga J;Morishima S;Morishima Y;Inoko H;Kulski JK;Shiina T
通讯作者：
Shiina T
影响因子：
3.2
作者：
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Parham P
影响因子：
45.3
作者：
Tsukasaki, Kunihiro;Hermine, Olivier;Watanabe, Toshiki
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Watanabe, Toshiki
影响因子：
45.3
作者：
Tsukasaki, Kunihiro;Utsunomiya, Atae;Tomonaga, Masao
通讯作者：
Tomonaga, Masao
影响因子：
46.9
作者：
Shukla SA;Rooney MS;Rajasagi M;Tiao G;Dixon PM;Lawrence MS;Stevens J;Lane WJ;Dellagatta JL;Steelman S;Sougnez C;Cibulskis K;Kiezun A;Hacohen N;Brusic V;Wu CJ;Getz G
通讯作者：
Getz G