癌症個人化醫療前瞻論壇 @ 台北喜來登 星月廳 (B2F)

Opening remarks: 賴瓊慧教授 (副研發長) 主持人: 王子豪醫師 (國外廠商contact him about STIP1)

閻紫宸教授: 台灣口腔癌病患新穎癒後生物標誌的發現與臨床意義

–Why OSCC: Taiwan has the oral cancer incidence in men worldwide

–Oral cavity cancer: incidence, survival and treatment

–廖俊達教授is the head of CGH HNSCC group leader (pastic surgeon is very important)

–OSCC 2-yr survival: CGMHLK vs all centers

–Clinical path of OSCC

    –全世界一樣的biologic phenotype: ECS positive (survival rate 30%, how to pick them up? )and LN meta

–Unanswered questions: (a) how unique is Taiwan’s OSCC? (b) Which genetic alterations can be used as the molecular markers for disease recurrence, metastasiss survival and second primary timor? (c) which targeted therapy can be used for OSCC patients?

–2000年以後是 molecular era, 2010 以後 是 immunotherapy era

–OSCC –LN meta 40% (positive) –? ECS positive (60%) –> 24%

–OSCC –LN meta 40% (positive) –? ECS negative (40%) –> 16%

–OSCC –LN meta 60% (negative) –Comparison 印度 （檳榔子 and no alcohol, 我們的是檳榔汁

–Outline of the study

Stage I: exploration (345 FFPE: ABI 45 core genes targeted based as deep as possible, at least 5-yr follow-up on 345 FFPE samples ; 其實發現妥善處理 應該到1996年的檢體都可用)

Stage II: verification

ultra-deep sequencing of all coding exns of 409 cancer genes using an ndependent cohort (currently, n=300

加入 miRNAs

conclusion: (1)80% found non-synmous mutations and 80% of them are on the top 

potential targetable genes

Stage II 90% found non-synmous mutations NOTCH1增加了

TP53 and NOTCH 與 TCGA相當

Pathwayss affected in OSCC (II)

–110 人 as base , 並以 image (free software abailable)DNA repair 

 

 

tage III: –compare to TCGA data, PI3KCA and TP53 是相當相似的 Notch1 似乎過低 Genetic alterations on prognosis: after 2004 we improve OSCC survival by “team combined care” 

–2015年: proton therapy 10 genes with mutation frequency > 2% were used to construct the OSCC prognostic gene panel with clinical outcomes –> 可以清清楚楚地把345個病人 (1996-2012 ) 分成兩群

–Internal validatio of OSCC prognostic gene panel: either by years (2004 as cutoff) or randomization

Q0: treated 病人還會有多少人嚼檳榔

Q1: CDKN2A (p16)  婁培人醫師: Taiwan p16 status: more mutations than what have been reporter in the Caucasians. (存疑)

                                廖仲達醫師: E6 E7 expressions are related to metastasis of oral cancer. 已發表蠻多篇相關papers

Q2: validation by TCGA data or Indian data 每一年3% 的survival patients 又會長出OSCC related: field cancerization NGS gene panel for developing primary tumor Stage 3: prognostic markers? 409 cancer genes in important signaling pathways cover 10 cancer genes and more than wp essential cancer pathways 

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胡松年博士: 消化性結腸炎癌病患者的基因變異圖譜分析

003-2011年來台多次 UC的病人後來成CRC的機率很高

whole genome : HiSeq 2000 and ion proton

數據庫: GWAS, CLINVAER, COSMIC, HGMD_

1 case clinical sample Exom-seq 100X germ-line 突變很高 -> DNA repair發生問題? 但四個數據庫裡頭都有的只有0個; 後改成任兩個有的則多落在germ-line突變

IBD 與 CRC 都有的 germlline mutations are similar to that reported by others DNA repair point mutations

CRC mutational landscape 1000 Genome

CHS (南方漢族人) vs CHB (北京漢族人)

208 WES and low coverage WGS –低頻mutation in DNA repair system — 7 DNA repair system 均有 — 106 genes

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