Details of Disease

General Information of Disease (ID: DISSABLZ)

• Disease Name: Lynch syndrome 1
• Synonyms: COCA1; colorectal cancer, hereditary nonpolyposis, type 1; Lynch syndrome 2; colon cancer, familial nonpolyposis, type 1; LYNCH syndrome I; Lynch syndrome type 1; HNPCC1; Lynch syndrome 1; hereditary nonpolyposis colorectal cancer type 1; Hereditary non-polyposis colon cancer type 1; Lynch 1 syndrome; familial non-polyposis colon cancer type 1
• Definition: Any Lynch syndrome in which the cause of the disease is a mutation in the MSH2 gene.
• Disease Hierarchy:
  DISPA49R: Hereditary nonpolyposis colon cancer
  DIS3HIWD: Autosomal dominant disease
  DISSABLZ: Lynch syndrome 1
• Disease Identifiers:
  MONDO ID: MONDO_0007356
  MESH ID: D003123
  UMLS CUI: C2936783
  OMIM ID: 120435
  MedGen ID: 423615

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDH1	TTLAWO6	Limited	Biomarker	[1]
CDKN1B	TTLGFVW	Limited	Biomarker	[2]
CHEK2	TT9ABMF	Limited	Biomarker	[3]
PTPRJ	TTWMKXP	Limited	Biomarker	[4]
SMARCA4	TTVQEZS	Limited	Biomarker	[5]
ATM	TTKBM7V	moderate	Biomarker	[6]
FBXO11	TT6G10V	Strong	CausalMutation	[7]
MLH1	TTISG27	Strong	Autosomal dominant	[8]
MLH1	TTISG27	Strong	CausalMutation	[9]
MSH2	TTCAWRT	Strong	CausalMutation	[10]
MSH2	TTCAWRT	Definitive	Autosomal dominant	[11]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
EPHX1	DELB4KP	Limited	Biomarker	[2]

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BARD1	OTTC0Z9Y	Limited	Biomarker	[12]
FAN1	OT1LM1HZ	Limited	Biomarker	[13]
MSH3	OTD3YPVL	Limited	Biomarker	[14]
MSH6	OT46FP09	Limited	CausalMutation	[7]
NFKBIZ	OTU728KS	Limited	Biomarker	[2]
PALB2	OT6DNDBG	Limited	Biomarker	[15]
RPS20	OTI8052R	Limited	Biomarker	[16]
SEMA4A	OT8901H3	Limited	Biomarker	[14]
EXO1	OTI87RS5	Disputed	Biomarker	[17]
MLH3	OT91PPBI	moderate	Biomarker	[18]
MLH1	OTG5XDD8	Strong	Autosomal dominant	[8]
PMS2	OTNLWTMI	Strong	CausalMutation	[7]
MSH2	OT10H1AB	Definitive	Autosomal dominant	[11]

References

• [1] Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis.Br J Cancer. 2016 Jan 19;114(2):199-206. doi: 10.1038/bjc.2015.347. Epub 2016 Jan 7.
• [2] Whole-exome sequencing identifies rare pathogenic variants in new predisposition genes for familial colorectal cancer. Genet Med. 2015 Feb;17(2):131-42. doi: 10.1038/gim.2014.89. Epub 2014 Jul 24.
• [3] Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.
• [4] Tumor Suppressor PTPRJ Is a Target of miR-155 in Colorectal Cancer.J Cell Biochem. 2017 Oct;118(10):3391-3400. doi: 10.1002/jcb.25995. Epub 2017 May 3.
• [5] The chromatin-remodeling enzyme BRG1 promotes colon cancer progression via positive regulation of WNT3A.Oncotarget. 2016 Dec 27;7(52):86051-86063. doi: 10.18632/oncotarget.13326.
• [6] The depletion of ATM inhibits colon cancer proliferation and migration via B562-mediated Chk1/p53/CD44 cascades.Cancer Lett. 2017 Apr 1;390:48-57. doi: 10.1016/j.canlet.2016.12.040. Epub 2017 Jan 14.
• [7] Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.
• [8] Mouse models for colorectal cancer. Oncogene. 1999 Sep 20;18(38):5325-33. doi: 10.1038/sj.onc.1203036.
• [9] Novel MLH1 mutations and a novel MSH2 polymorphism identified by SSCP and DHPLC in Portuguese HNPCC families.Hum Mutat. 2003 Nov;22(5):419-20. doi: 10.1002/humu.9192.
• [10] Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations.PLoS Genet. 2017 Apr 19;13(4):e1006739. doi: 10.1371/journal.pgen.1006739. eCollection 2017 Apr.
• [11] A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish HNPCC kindred: implications for clinical screening. J Med Genet. 1999 Oct;36(10):790-3. doi: 10.1136/jmg.36.10.792.
• [12] Expression of an Oncogenic BARD1 Splice Variant Impairs Homologous Recombination and Predicts Response to PARP-1 Inhibitor Therapy in Colon Cancer.Sci Rep. 2016 May 20;6:26273. doi: 10.1038/srep26273.
• [13] Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks to prevent genome instability.Science. 2016 Feb 19;351(6275):846-9. doi: 10.1126/science.aad5634. Epub 2016 Jan 21.
• [14] Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis. Am J Hum Genet. 2016 Aug 4;99(2):337-51. doi: 10.1016/j.ajhg.2016.06.015. Epub 2016 Jul 28.
• [15] Inherited DNA-Repair Defects in Colorectal Cancer.Am J Hum Genet. 2018 Mar 1;102(3):401-414. doi: 10.1016/j.ajhg.2018.01.018. Epub 2018 Feb 22.
• [16] Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in an Analysis of Families and Patients-a Systematic Review.Gastroenterology. 2017 Jan;152(1):75-77.e4. doi: 10.1053/j.gastro.2016.09.041. Epub 2016 Oct 3.
• [17] Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients.BMC Med Genet. 2014 Jan 31;15:17. doi: 10.1186/1471-2350-15-17.
• [18] Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome.Genes Chromosomes Cancer. 2009 Apr;48(4):340-50. doi: 10.1002/gcc.20644.