HNPCC 的的的的的 的的的的的的的的的的 的的的的 的的的 2010-4-29
研究背景介绍• 何为 HNPCC ?• 常染色体显性遗传病; 5-10% 发生率; MMR 缺陷引起
• 如何研究?• 临床标准;选择 MLH1 和 MSH2 基因筛查突变
• 研究现状• 欧洲多,亚洲少• 90% 突变出现在 MLH1 和 MSH2• 无热点突变
研究背景介绍• 临床标准• Amsterdam I&II ; Bethesda ;
• 数据库• 最权威—— InSight (http://www.insight-group.org)
• 研究的意义是什么?• 遗传性疾病,早预防早治疗• 中国研究较少• 希望找到亚洲或中国的热点突变• 为中国的临床检测提供指导
Amsterdam I&II criteria Bethesda criteria Alln(%) 15(15.3%) 83(84.7%) 98(100%)Age(median, range) years 48.1(35-67) 47.6(19-82) 47.7(19-82)Sex n(%) male 12(80.0%) 45(54.2%) 57(58.2%) female 3(20.0%) 38(45.8%) 41(41.8%)Location n(%) Ascending colon 5(23.8%) 20(20.4%) 25(21.0%) Hepatic flexure 2(9.5%) 2(2.0%) 4(3.4%) Transverse colon 2(9.5%) 8(8.2%) 10(8.4%) Splenic flexure 2(9.5%) 1(1.0%) 3(2.5%) Descending colon 4(19.0%) 8(8.2%) 12(10.1%) Sigmoid colon 3(14.3%) 15(15.3%) 18(15.1%) Rectum 3(14.3%) 44(44.9%) 47(39.5%)Multiple cancer synchronous tumours 3(20.0%) 3(3.6%) 6(6.1%)
metachronous tumour 4(26.7%) 17(20.5%) 21(21.4%)Pathology adenocarcinoma 13(86.7%) 69(83.1%) 82(83.7%) mucinous carcinoma 2(13.3%) 11(13.2%) 13(13.3%) Others 0(0.0%) 3(3.6%) 3(3.1%)Family history 15 51 66
同时异时肿瘤发生率高
粘液腺癌 >10%
• 31 CRC happened, 11 were left side and 20 were right (64.5% vs. 35.5%),
• 20 related cancers happened, most of them were gastric cancer and endometrial carcinoma, 5 each
(25%).
Family ID
CRC number
CRC frequency
Cancer number
Cancer frequency Male Female
Onset age of CRC
Onset age of cancer
Multiple primary
CRC
Multiple primary tumors
Right site
Left site
Extracolonic cancer (type)
Mucinous carcinoma
H9 4 6 4 6 3 1 48 48 2 2 5 1 0 0H76 5 5 5 5 4 1 37 37 0 0 1 4 0 0
H86 1 2 3 5 2 1 47 47 1 1 1 1 3(1St, 1Es, 1E) 1
H88 1 1 3 3 3 0 19 19 0 0 1 0 2(2L) 0H166 4 5 4 5 2 2 36 36 1 1 2 3 0 0H167 4 6 5 7 3 2 29 29 2 2 1 5 1(1E) 0
H224 1 1 5 7 2 3 44 51 0 2 0 1 6(2St, 2E, 2Br) 0
H231 1 1 2 3 1 1 47 44 0 1 0 1 2(1L, 1Br) 0H236 3 3 3 4 1 2 40 40 0 1 0 3 1(1E) 1
H245 1 1 3 6 1 2 56 50 0 1 0 15(2St, 1Li, 1L,
1O)0
突变Family
ID
MutationClinical criteria
Having been reported (times)Gene Exon Nucleotide Consequence Type
H9 MSH2 1 c.23C>T p.Thr8Met Missense Amsterdam Yes (5)
H76 MLH1 2c.157del GAGG
Frameshift Amsterdam No
H86 MLH1 1 c.-64G>T Uncertain Bethesda NoH88 MSH2 7 c.1168C>T p.Phe390Leu Missense Bethesda Yes (34)
H166 MLH1 8 c.655A>G p.Ile219Val Missense Amsterdam Yes (224)
H167 MLH1 17 c.1989G>AAberrant splicing
Amsterdam Yes (2)
H224 MLH1 19 c.2159insG FrameshiftBethesda
NoMSH2 7 c.1168C>T p.Phe390Leu Missense Yes (34)
H231 MSH2 7 c.1168C>T p.Phe390Leu Missense Bethesda Yes (34)H236 MLH1 18 c.2042C>T p.Ala681Val Missense Bethesda Yes (1)H245 MSH2 7 c.1168C>T p.Phe390Leu Missense Bethesda Yes (34)
该患者同时有两个突变,且满足复旦推荐标准
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