Striking heterogeneity of somatic L1 retrotransposition in single normal and cancerous gastrointestinal cells.
Striking heterogeneity of somatic L1 retrotransposition in single normal and cancerous gastrointestinal cells.
复制标题
单个正常和癌性胃肠道细胞中体细胞 L1 逆转录转座的惊人异质性。
DOI：
10.1073/pnas.2019450117
复制
发表时间：
2020
影响因子：
11.1
通讯作者：
KazazianJr,HaigH
中科院分区：
文献类型：
--
作者：
Yamaguchi,Katsumi;Soares,AlishaO;Goff,LoyalA;Talasila,Anjali;Choi,JungbinA;Ivenitsky,Daria;Karma,Sadik;Brophy,Benjamin;Devine,ScottE;Meltzer,StephenJ;KazazianJr,HaigH
体细胞LINE-1（L1）逆转录转座已在早期胚胎、成人脑和胃肠道（GI）以及许多癌症（包括上皮GI肿瘤）中检测到。我们以前发现许多体细胞L1插入配对正常和胃肠道癌组织。在这里，使用一种改进的方法，单细胞分析体细胞L1插入，我们研究了结肠腺癌，胰腺癌和胃癌，并发现了一个变量的体细胞L1插入在同一类型的肿瘤从病人到病人。我们检测到没有体细胞L1插入的单细胞中的10个肿瘤研究的5。在三个肿瘤中，通过FACS检测到非整倍体细胞。在一个胰腺肿瘤中，非整倍体肿瘤细胞中的L1插入比整倍体肿瘤细胞中的多得多。在一个胃癌中，非整倍体和整倍体细胞都含有大量可能的克隆插入。然而，在第二个胃癌与非整倍体细胞，没有体细胞L1插入被发现。我们认为，当细胞环境是有利的逆转录，非整倍体倾向于肿瘤细胞L1插入，逆转录可能发生在从整倍体到非整倍体的过渡。17%的插入也存在于正常细胞中，与GI肿瘤患者正常组织的基因组DNA中的发现相似。我们提供的证据表明：1）相同类型肿瘤中L1插入的数量是高度可变的，2）GI癌组织中的大多数体细胞L1插入在正常组织中不存在，3）在某些条件下，体细胞L1逆转录转座表现出在非整倍体细胞中发生的倾向。
Somatic LINE-1 (L1) retrotransposition has been detected in early embryos, adult brains, and the gastrointestinal (GI) tract, and many cancers, including epithelial GI tumors. We previously found numerous somatic L1 insertions in paired normal and GI cancerous tissues. Here, using a modified method of single-cell analysis for somatic L1 insertions, we studied adenocarcinomas of colon, pancreas, and stomach, and found a variable number of somatic L1 insertions in tumors of the same type from patient to patient. We detected no somatic L1 insertions in single cells of 5 of 10 tumors studied. In three tumors, aneuploid cells were detected by FACS. In one pancreatic tumor, there were many more L1 insertions in aneuploid than in euploid tumor cells. In one gastric cancer, both aneuploid and euploid cells contained large numbers of likely clonal insertions. However, in a second gastric cancer with aneuploid cells, no somatic L1 insertions were found. We suggest that when the cellular environment is favorable to retrotransposition, aneuploidy predisposes tumor cells to L1 insertions, and retrotransposition may occur at the transition from euploidy to aneuploidy. Seventeen percent of insertions were also present in normal cells, similar to findings in genomic DNA from normal tissues of GI tumor patients. We provide evidence that: 1) The number of L1 insertions in tumors of the same type is highly variable, 2) most somatic L1 insertions in GI cancer tissues are absent from normal tissues, and 3) under certain conditions, somatic L1 retrotransposition exhibits a propensity for occurring in aneuploid cells.