第二等位基因：理解散发性和遗传性结直肠肿瘤发生时间的关键。
The Second Allele: A Key to Understanding the Timing of Sporadic and Hereditary Colorectal Tumorigenesis.
机构信息
Northwestern Medicine Digestive Health Center, Chicago, IL 60611, USA.
Invitae, San Francisco, CA 94103, USA.
出版信息
Genes (Basel). 2021 Sep 26;12(10):1515. doi: 10.3390/genes12101515.
Abstract
Our understanding of the molecular basis of colorectal neoplasia is derived from Mendelian genetics, with tumor suppressor genes contributing more to the deregulation of growth than oncogenes. In patients with hereditary syndromes, expression of one allele of a key tumor suppressor gene is absent at birth. The loss of the expression of the second allele precipitates tumorigenesis. However, there are multiple ways in which the expression of the second allele of a tumor suppressor gene is lost. Here, we review these ways and their possible effect on phenotype.
摘要
我们对结直肠肿瘤发生分子基础的理解源自孟德尔遗传学，抑癌基因比癌基因在生长失控中发挥更大的作用。在遗传性综合征患者中，出生时就缺失一个关键抑癌基因的一个等位基因的表达。第二个等位基因的表达缺失会引发肿瘤发生。然而，抑癌基因的第二个等位基因的表达缺失有多种方式。在这里，我们回顾这些方式及其对表型可能产生的影响。
相似文献
1
The Second Allele: A Key to Understanding the Timing of Sporadic and Hereditary Colorectal Tumorigenesis.第二等位基因：理解散发性和遗传性结直肠肿瘤发生时间的关键。
Genes (Basel). 2021 Sep 26;12(10):1515. doi: 10.3390/genes12101515.
2
Promoter hypermethylation leads to decreased APC mRNA expression in familial polyposis and sporadic colorectal tumours, but does not substitute for truncating mutations.启动子高甲基化导致家族性腺瘤性息肉病和散发性结直肠癌中APC信使核糖核酸表达降低，但不能替代截短突变。
Exp Mol Pathol. 2008 Dec;85(3):201-6. doi: 10.1016/j.yexmp.2008.09.006. Epub 2008 Oct 11.
3
Cross-species comparison of human and mouse intestinal polyps reveals conserved mechanisms in adenomatous polyposis coli (APC)-driven tumorigenesis.人类和小鼠肠道息肉的跨物种比较揭示了腺瘤性息肉病 coli（APC）驱动的肿瘤发生中的保守机制。
Am J Pathol. 2008 May;172(5):1363-80. doi: 10.2353/ajpath.2008.070851. Epub 2008 Apr 10.
4
Ovarian steroid cell tumor with biallelic adenomatous polyposis coli inactivation in a patient with familial adenomatous polyposis.家族性腺瘤性息肉病患者中存在双侧腺瘤性结肠息肉病基因灭活的卵巢类固醇细胞瘤。
Genes Chromosomes Cancer. 2012 Mar;51(3):283-9. doi: 10.1002/gcc.20953. Epub 2011 Nov 25.
5
Gastrointestinal polyposis syndromes.胃肠道息肉病综合征
Curr Mol Med. 2007 Feb;7(1):29-46. doi: 10.2174/156652407779940404.
6
A targeted constitutive mutation in the APC tumor suppressor gene underlies mammary but not intestinal tumorigenesis.APC肿瘤抑制基因中的靶向组成性突变是乳腺肿瘤发生的基础，但不是肠道肿瘤发生的基础。
PLoS Genet. 2009 Jul;5(7):e1000547. doi: 10.1371/journal.pgen.1000547. Epub 2009 Jul 3.
7
Loss of a single Hic1 allele accelerates polyp formation in Apc(Δ716) mice.单个 Hic1 等位基因的缺失会加速 Apc(Δ716) 小鼠的息肉形成。
Oncogene. 2011 Jun 9;30(23):2659-69. doi: 10.1038/onc.2010.633. Epub 2011 Feb 7.
8
Molecular mechanism of adenomatous polyposis coli-induced blockade of base excision repair pathway in colorectal carcinogenesis.腺瘤性结肠息肉病蛋白在结直肠癌发生过程中诱导碱基切除修复途径阻断的分子机制。
Life Sci. 2015 Oct 15;139:145-52. doi: 10.1016/j.lfs.2015.08.019. Epub 2015 Sep 1.
9
Familial adenomatous polyposis associated with multiple endocrine neoplasia type 1-related tumors and thyroid carcinoma: a case report with clinicopathologic and molecular analyses.家族性腺瘤性息肉病合并多发性内分泌肿瘤1型相关肿瘤及甲状腺癌：一例临床病理及分子分析病例报告
Am J Surg Pathol. 2002 Jan;26(1):103-10. doi: 10.1097/00000478-200201000-00014.
10
Difference in the role of loss of heterozygosity at 10p15 (KLF6 locus) in colorectal carcinogenesis between sporadic and familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer patients.散发性、家族性腺瘤性息肉病以及遗传性非息肉病性结直肠癌患者中，10p15（KLF6基因座）杂合性缺失在结直肠癌发生过程中的作用差异。
Oncology. 2006;71(1-2):131-5. doi: 10.1159/000100523. Epub 2007 Mar 9.
引用本文的文献
1
Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand.外显子组测序揭示泰国最南端地区乳腺癌患者的新型种系变异。
J Pers Med. 2023 Nov 9;13(11):1587. doi: 10.3390/jpm13111587.
本文引用的文献
1
Defining eligible patients for allele-selective chemotherapies targeting NAT2 in colorectal cancer.定义针对结直肠癌中 NAT2 的等位基因选择性化疗的合格患者。
Sci Rep. 2020 Dec 31;10(1):22436. doi: 10.1038/s41598-020-80288-z.
2
Exploiting loss of heterozygosity for allele-selective colorectal cancer chemotherapy.利用杂合性缺失进行针对结直肠癌的等位基因选择性化疗。
Nat Commun. 2020 Mar 11;11(1):1308. doi: 10.1038/s41467-020-15111-4.
3
Update on the World Health Organization Criteria for Diagnosis of Serrated Polyposis Syndrome.世界卫生组织锯齿状息肉病综合征诊断标准的更新
Gastroenterology. 2020 May;158(6):1520-1523. doi: 10.1053/j.gastro.2019.11.310. Epub 2020 Jan 23.
4
Sessile Serrated Polyposis: Not an Inherited Syndrome?无蒂锯齿状息肉：非遗传性综合征？
Dis Colon Rectum. 2020 Feb;63(2):183-189. doi: 10.1097/DCR.0000000000001537.
5
DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways.BRAF 介导的 TET 沉默导致的 DNA 甲基化不稳定性和生活方式暴露将结肠癌途径分开。
Clin Epigenetics. 2019 Dec 16;11(1):196. doi: 10.1186/s13148-019-0791-1.
6
Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development.肠道微生物组对结肠上皮细胞的基因组和表观基因组的影响：对结直肠癌发展的贡献。
Genome Med. 2019 Feb 25;11(1):11. doi: 10.1186/s13073-019-0621-2.
7
Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: implications for therapeutic targeting.APC 肿瘤抑制蛋白的功能依赖和不依赖于经典 WNT 信号通路：对治疗靶点的影响。
Cancer Metastasis Rev. 2018 Mar;37(1):159-172. doi: 10.1007/s10555-017-9725-6.
8
NTHL1 and MUTYH polyposis syndromes: two sides of the same coin?NTHL1 和 MUTYH 息肉综合征：同一枚硬币的两面？
J Pathol. 2018 Feb;244(2):135-142. doi: 10.1002/path.5002. Epub 2017 Dec 14.
9
Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer.不同的肠道微生物群模式与结直肠癌的共识分子亚型相关。
Sci Rep. 2017 Sep 14;7(1):11590. doi: 10.1038/s41598-017-11237-6.
10
Haploinsufficient tumor suppressor genes.单倍体不足的肿瘤抑制基因。
Adv Med Biol. 2017;118:83-122.
Zotero 插件