Whole-exome sequencing identifies variants in invasive pituitary adenomas.
Whole-exome sequencing identifies variants in invasive pituitary adenomas.
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全外显子组测序识别侵袭性垂体腺瘤的变异
DOI：
10.3892/ol.2016.5029
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发表时间：
2016-10
期刊：
影响因子：
2.9
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Lan X;Gao H;Wang F;Feng J;Bai J;Zhao P;Cao L;Gui S;Gong L;Zhang Y
垂体腺瘤表现出广泛的行为。预测垂体腺瘤的侵袭性或恶性行为仍然具有挑战性。本研究的目的是确定与散发性垂体腺瘤侵袭性相关的遗传异常。本研究采用全外显子组测序法对6例侵袭性垂体腺瘤（IPA）和6例非侵袭性垂体腺瘤（nIPA）的外显子组进行测序。通过双脱氧核苷酸测序确认变异，并在另外28个垂体腺瘤中评估候选驱动基因。共鉴定出15种变异，主要与血管生成、代谢、细胞周期阶段、细胞组分组织、细胞骨架和细胞水平上的生物发生免疫相关，包括13种以单核苷酸变异形式出现的变异和2种由插入组成的变异。弥漫性泛细支气管炎关键区1（DPCR 1）、KIAA 0226、粘病毒（流感病毒）抗性，富含脯氨酸的蛋白BstNI亚家族3，含有PR结构域2，具有ZNF结构域，RIZ 1（PRDM 2），含有PR结构域8（PRDM 8），SPAN X家族成员N2（SPAN XN 2），IPA标本中TRIO和F-actin结合蛋白和锌指蛋白717比nIPA标本减少50%。特别是，IPA标本中的DPCR 1、PRDM 2、PRDM 8和SPAN XN 2 mRNA水平比nIPA标本低约4倍（分别为P=0.003、0.007、0.009和0.004）。牙本质涎磷蛋白、EGF样结构域7（EGFL 7）、低密度脂蛋白受体相关蛋白1B和动力蛋白、轴丝组装因子1（LRRC 50）的mRNA水平在IPA中均高于nIPA（P分别为0.041、0.037、0.022和0.013）。此外，PRDM 2表达降低与肿瘤复发相关。本研究的结果表明，DPCR 1，EGFL 7，PRDM家族和LRRC 50在垂体腺瘤的肿瘤发生的修改器，最有可能有助于发展的嗜酸性细胞的变化和侵袭性肿瘤表型。
Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F-actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor-related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of tumorigenesis, and most likely contribute to the development of oncocytic change and to the invasive tumor phenotype.
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影响因子：
10.5
作者：
Kajimura, Shingo;Seale, Patrick;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
胰腺神经内分泌肿瘤中经常改变DAXX/ATRX，MEN1和MTOR途径基因。
DOI：
10.1126/science.1200609
发表时间：
2011-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jiao Y;Shi C;Edil BH;de Wilde RF;Klimstra DS;Maitra A;Schulick RD;Tang LH;Wolfgang CL;Choti MA;Velculescu VE;Diaz LA Jr;Vogelstein B;Kinzler KW;Hruban RH;Papadopoulos N
通讯作者：
Papadopoulos N
影响因子：
2.5
作者：
Lee, Jin Sol;Bae, Joon Seol;Shin, Hyoung Doo
通讯作者：
Shin, Hyoung Doo
表皮生长因子样结构域7是内皮谱系和活性血管生成的标记。
影响因子：
1.5
作者：
Bambino, Kathryn;Lacko, Lauretta A.;Hajjar, Katherine A.;Stuhlmann, Heidi
通讯作者：
Stuhlmann, Heidi
DOI：
10.1126/science.1206923
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Agrawal N;Frederick MJ;Pickering CR;Bettegowda C;Chang K;Li RJ;Fakhry C;Xie TX;Zhang J;Wang J;Zhang N;El-Naggar AK;Jasser SA;Weinstein JN;Treviño L;Drummond JA;Muzny DM;Wu Y;Wood LD;Hruban RH;Westra WH;Koch WM;Califano JA;Gibbs RA;Sidransky D;Vogelstein B;Velculescu VE;Papadopoulos N;Wheeler DA;Kinzler KW;Myers JN
通讯作者：
Myers JN