Association of a novel point mutation in MSH2 gene with familial multiple primary cancers
文献类型：期刊论文
| 作者 | Hu, Hai1,2,5; Jiao, Feng2; Han, Ting2; Zhuo, Meng2; Cui, Jiujie2; Wang, Liwei2; Li, Hong3; Li, Yixue3; Li, Yixue4; , |
| 刊名 | JOURNAL OF HEMATOLOGY & ONCOLOGY
 |
| 出版日期 | 2017 |
| 卷号 | 10期号:-页码:158 |
| 关键词 | Lynch syndrome Cancer landscape MSH2 Carcinogenesis Multiple primary cancers |
| ISSN号 | 1756-8722 |
| DOI | 10.1186/s13045-017-0523-y |
| 文献子类 | Article |
| 英文摘要 | Background: Multiple primary cancers (MPC) have been identified as two or more cancers without any subordinate relationship that occur either simultaneously or metachronously in the same or different organs of an individual. Lynch syndrome is an autosomal dominant genetic disorder that increases the risk of many types of cancers. Lynch syndrome patients who suffer more than two cancers can also be considered as MPC; patients of this kind provide unique resources to learn how genetic mutation causes MPC in different tissues. Methods: We performed a whole genome sequencing on blood cells and two tumor samples of a Lynch syndrome patient who was diagnosed with five primary cancers. The mutational landscape of the tumors, including somatic point mutations and copy number alternations, was characterized. We also compared Lynch syndrome with sporadic cancers and proposed a model to illustrate the mutational process by which Lynch syndrome progresses to MPC. Results: We revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent. Integrative analysis showed that truncating mutations of DNA mismatch repair (MMR) genes were significantly enriched in the patient. A mutation progress model that included germline mutations of MMR genes, double hits of MMR system, mutations in tissue-specific driver genes, and rapid accumulation of additional passenger mutations was proposed to illustrate how MPC occurs in Lynch syndrome patients. Conclusion: Our findings demonstrate that both germline and somatic alterations are driving forces of carcinogenesis, which may resolve the carcinogenic theory of Lynch syndrome. |
| 学科主题 | Oncology ; Hematology |
| WOS关键词 | COMPREHENSIVE MOLECULAR CHARACTERIZATION ; BREAST-CANCER ; LYNCH-SYNDROME ; PRIMARY MALIGNANCIES ; COLORECTAL CANCERS ; SEQUENCING DATA ; CARCINOMA ; MECHANISMS ; SIGNATURES ; VARIANTS |
| 语种 | 英语 |
| WOS记录号 | WOS:000412071900001 |
| 出版者 | BIOMED CENTRAL LTD |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/909]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Pancreat Canc Ctr, Shanghai 201620, Peoples R China, 2.Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp,Sch Med, Dept Oncol,State Key Lab Oncogenes & Related Gene, Shanghai 201620, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai 200031, Peoples R China; 4.Shanghai Ctr Bio Informat Technol, 1278 Keyuan Rd, Shanghai 201203, Peoples R China; 5.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Med Oncol, Shanghai 201620, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Hu, Hai,Jiao, Feng,Han, Ting,et al. Association of a novel point mutation in MSH2 gene with familial multiple primary cancers[J]. JOURNAL OF HEMATOLOGY & ONCOLOGY,2017,10(-):158. |
| APA | Hu, Hai.,Jiao, Feng.,Han, Ting.,Zhuo, Meng.,Cui, Jiujie.,...&,.(2017).Association of a novel point mutation in MSH2 gene with familial multiple primary cancers.JOURNAL OF HEMATOLOGY & ONCOLOGY,10(-),158. |
| MLA | Hu, Hai,et al."Association of a novel point mutation in MSH2 gene with familial multiple primary cancers".JOURNAL OF HEMATOLOGY & ONCOLOGY 10.-(2017):158. |
入库方式： OAI收割
来源：上海营养与健康研究所
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