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CLC number: R735.3

On-line Access: 2019-01-07

Received: 2018-02-27

Revision Accepted: 2018-06-26

Crosschecked: 2018-12-05

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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.1 P.105-108

http://doi.org/10.1631/jzus.B1800105


A frameshift mutation in exon 19 of MLH1 in a Chinese Lynch syndrome family: a pedigree study#


Author(s):  Qiao-Qi Sui, Wu Jiang, Xiao-Dan Wu, Yi-Hong Ling, Zhi-Zhong Pan, Pei-Rong Ding

Affiliation(s):  Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; more

Corresponding email(s):   panzhzh@sysucc.org.cn, dingpr@sysucc.org.cn

Key Words:  Lynch syndrome, DNA mismatch repair, Frameshift mutation


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Qiao-Qi Sui, Wu Jiang, Xiao-Dan Wu, Yi-Hong Ling, Zhi-Zhong Pan, Pei-Rong Ding. A frameshift mutation in exon 19 of MLH1 in a Chinese Lynch syndrome family: a pedigree study#[J]. Journal of Zhejiang University Science B, 2019, 20(1): 105-108.

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pages="105-108",
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publisher="Zhejiang University Press & Springer",
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Abstract: 
lynch syndrome (LS), an autosomal dominantly inherited disease previously known as hereditary non-polyposis colorectal cancer (HNPCC), leads to a high risk of colorectal cancer (CRC) as well as malignancy at certain sites including endometrium, ovary, stomach, and small bowel (Hampel et al., 2008; Lynch et al., 2009). Clinically, LS is considered the most common hereditary CRC-predisposing syndrome, accounting for about 3% of all CRC cases (Popat et al., 2005). LS is associated with mutations of DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, PMS2, and EPCAM (Ligtenberg et al., 2009; Lynch et al., 2009), which can trigger a high frequency of replication errors in both microsatellite regions and repetitive sequences in the coding regions of various cancer-related genes. Immunohistochemistry (IHC) tests followed by genetic analysis of these mutations play a significant role in diagnosis, treatment determination, and therapeutic response prediction of LS (Lynch et al., 2009; Alex et al., 2017; Ryan et al., 2017). Here, we report substitution of one base-pair in exon 1 of MLH3 (c.1397C>A) and a frameshift mutation in exon 19 of MLH1 (c.2250_2251ins AA) in a 43-year-old Chinese male with an LS pedigree.

一个中国Lynch综合征家系携带的MLH1基因第19号外显子移码突变:一项家系研究

目的:寻找一个Lynch综合征患者所在家系携带的DNA错配修复基因突变,探讨各突变对肿瘤发生发展 的影响.
创新点:MLH1的第19号外显子c.2250_2251insAA移码突变既往被认为是意义未名突变,而我们的研究为明确该突变的致病意义提供了依据.另外,我们首次报道了MLH3基因第1号外显子c.1397C>A突变.该突变有可能使Lynch综合征患者的发病年龄提前.
方法:运用免疫组织化学技术检测家系先证者肿瘤组织中错配修复基因蛋白的缺失情况,使用二代测序技术通过先证者血标本明确患者所携带的突变.同时运用Sanger法检测家系其他成员该突变的携带情况以明确突变对肿瘤发生发展的影响.
结论:我们在患者体内发现MLH1基因第19号外显子移码突变(c.2250_2251insAA)以及 MLH3基因第1号外显子c.1397C>A突变.在患者家系中,我们仅检测到有MLH1突变,因此该突变极有可能为致病突变.

关键词:Lync综合征;家系;DNA错配修复基因;置换;移码突变

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Reference

[1]Alex AK, Siqueira S, Coudry R, et al., 2017. Response to chemotherapy and prognosis in metastatic colorectal cancer with DNA deficient mismatch repair. Clin Colorectal Cancer, 16(3):228-239.

[2]Chen PC, Dudley S, Hagen W, et al., 2005. Contributions by mutl homologues Mlh3 and Pms2 to DNA mismatch repair and tumor suppression in the mouse. Cancer Res, 65(19):8662-8670.

[3]Chen PC, Kuraguchi M, Velasquez J, et al., 2008. Novel roles for MLH3 deficiency and TLE6-like amplification in DNA mismatch repair-deficient gastrointestinal tumorigenesis and progression. PLoS Genet, 4(6):e1000092.

[4]Dominguez-Valentin M, Nilbert M, Wernhoff P, et al., 2013. Mutation spectrum in south american lynch syndrome families. Hered Cancer Clin Pract, 11(1):18.

[5]Hampel H, Frankel WL, Martin E, et al., 2008. Feasibility of screening for lynch syndrome among patients with colorectal cancer. J Clin Oncol, 26(35):5783-5788.

[6]Hienonen T, Laiho P, Salovaara R, et al., 2003. Little evidence for involvement of MLH3 in colorectal cancer predisposition. Int J Cancer, 106(2):292-296.

[7]Kim KH, Kim JY, Oh SI, et al., 2009. A novel germline mutation of hMLH1 in a korean hereditary non-polyposis colorectal cancer family. Int J Oncol, 34(5):1313-1318.

[8]Korhonen MK, Vuorenmaa E, Nyström M, 2008. The first functional study of MLH3 mutations found in cancer patients. Genes Chromosomes Cancer, 47(9):803-809.

[9]Ligtenberg MJL, Kuiper RP, Chan TL, et al., 2009. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet, 41(1):112-117.

[10]Lynch HT, Lynch PM, Lanspa SJ, et al., 2009. Review of the lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet, 76(1):1-18.

[11]Mohd AB, Palama B, Nelson SE, et al., 2006. Truncation of the C-terminus of human MLH1 blocks intracellular stabilization of PMS2 and disrupts DNA mismatch repair. DNA Repair, 5(3):347-361.

[12]Popat S, Hubner R, Houlston RS, 2005. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol, 23(3):609-618.

[13]Ryan E, Sheahan K, Creavin B, et al., 2017. The current value of determining the mismatch repair status of colorectal cancer: a rationale for routine testing. Crit Rev Oncol Hematol, 116:38-57.

[14]Sheng JQ, Fu L, Sun ZQ, et al., 2008. Mismatch repair gene mutations in Chinese HNPCC patients. Cytogenet Genome Res, 122(1):22-27.

[15]List of electronic supplementary materials

[16]Fig. S1 Sequencing of the proband

[17]Fig. S2 Sequencing of the patients of the Lynch syndrome pedigree

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