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首页 » 生物研究 » Clin Chem:科学家揭示阑尾癌基因突变蓝图

Clin Chem:科学家揭示阑尾癌基因突变蓝图

来源:生物谷 2014-05-14 08:58

2014年5月14日讯 /生物谷BIOON/--使用新一代DNA测序技术,Dartmouth科学家已经确定了阑尾癌潜在关键突变。他们的研究“Molecular Profiling of Appendiceal Epithelial Tumors Using Massively Parallel Sequencing to Identify Somatic Mutations”发表在Clinical Chemistry杂志上。当癌症类型特定突变被确定,患者可以选用化疗或其他靶向这些突变的药物进行处理。

两种类型阑尾肿瘤--低度恶性阑尾黏液性肿瘤(LAMN)和腺癌的分子生物学鲜为人知,但低度恶性阑尾黏液性肿瘤(LAMN)和腺癌都可以导致腹膜假性黏液瘤(PMP),其中癌细胞沿着腹部壁失控生长。

Dartmouth病理学家研究38 例LAMN和腺癌(其中有些已经发展到PMP)标本,以寻找可能负责异常细胞生长共同的遗传错误。使用AmpiSeq Hotspot Cancer Panel v2测序组织样品,此测序方法经常被使用测序肺腺癌,黑色素瘤,结肠癌和胶质瘤等,Gregory Tsongalis博士说:考察肿瘤突变性状有可能以积极的方式显著改变病人的结果。

KRAS和GNAS突变是研究发现最常见的改变,在四个样本类型中,额外的突变也被确定(即LAMN的AKT1,APC,JAK3,MET,PIK3CA,RB1和STK11;腺癌的TP53,GNAS和RB1)。Tsongalis表示:未来新的治疗方法可能能够针对这些突变。(生物谷Bioon.com)

Molecular Profiling of Appendiceal Epithelial Tumors Using Massively Parallel Sequencing to Identify Somatic Mutations.

Xiaoying Liu, Kabir Mody, Francine B. De Abreu, J. Marc Pipas, Jason D. Peterson, Torrey L. Gallagher, Arief A. Suriawinata, Gregory H. Ripple, Kathryn C. Hourdequin, Kerrington D. Smith, Richard J. Barth, Jr., Thomas A. Colacchio, Michael J. Tsapakos, Bassem I. Zaki, Timothy B. Gardner, Stuart R. Gordon, Christopher I. Amos, Wendy A. Wells, and Gregory J. Tsongalis.

Background: Some epithelial neoplasms of the appendix, including low-grade appendiceal mucinous neoplasm and adenocarcinoma, can result in pseudomyxoma peritonei (PMP). Little is known about the mutational spectra of these tumor types and whether mutations may be of clinical significance with respect to therapeutic selection. In this study, we identified somatic mutations using the Ion Torrent AmpliSeq Cancer Hotspot Panel v2.

Methods: Specimens consisted of 3 nonneoplastic retention cysts/mucocele, 15 low-grade mucinous neoplasms (LAMNs), 8 low-grade/well-differentiated mucinous adenocarcinomas with pseudomyxoma peritonei, and 12 adenocarcinomas with/without goblet cell/signet ring cell features. Barcoded libraries were prepared from up to 10 ng of extracted DNA and multiplexed on single 318 chips for sequencing. Data analysis was performed using Golden Helix SVS. Variants that remained after the analysis pipeline were individually interrogated using the Integrative Genomics Viewer.

Results: A single Janus kinase 3 (JAK3) mutation was detected in the mucocele group. Eight mutations were identified in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) genes among LAMN samples. Additional gene mutations were identified in the AKT1 (v-akt murine thymoma viral oncogene homolog 1), APC (adenomatous polyposis coli), JAK3, MET (met proto-oncogene), phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA), RB1 (retinoblastoma 1), STK11 (serine/threonine kinase 11), and tumor protein p53 (TP53) genes. Among the PMPs, 6 mutations were detected in the KRAS gene and also in the GNAS, TP53, and RB1 genes. Appendiceal cancers showed mutations in the APC, ATM (ataxia telangiectasia mutated), KRAS, IDH1 [isocitrate dehydrogenase 1 (NADP+)], NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog], PIK3CA, SMAD4 (SMAD family member 4), and TP53 genes.

Conclusions: Our results suggest molecular heterogeneity among epithelial tumors of the appendix. Next generation sequencing efforts have identified mutational spectra in several subtypes of these tumors that may suggest a phenotypic heterogeneity showing mutations that are relevant for targeted therapies.

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