Characterizing the prevalence of chromosome instability in interval colorectal cancer.
Characterizing the prevalence of chromosome instability in interval colorectal cancer.
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DOI：
10.1016/j.neo.2015.02.001
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发表时间：
2015-03
期刊：
影响因子：
4.8
通讯作者：
McManus, K. J.
中科院分区：
文献类型：
--
作者：
Cisyk, A. L.;Penner-Goeke, S.;Lichtensztejn, Z.;Nugent, Z.;Wightman, R. H.;Singh, H.;McManus, K. J.
大部分结肠直肠癌（CRC）是间隔CRC（I-CRC;即，结肠镜检查后不久诊断的CRC）。染色体不稳定性（CIN）定义为获得或丢失完整染色体/大染色体片段的比率增加，在85%的非遗传性CRC中观察到。CIN对I-CRC病因学的贡献仍然未知。我们建立了一种荧光原位杂交（FISH）方法，通过计数特定染色体来表征CIN，并确定了I-CRC和对照（散发性）CRC人群中数值CIN的患病率。使用基于人口的马尼托巴卫生行政数据库和马尼托巴癌症登记处，我们确定了年龄，性别和结肠部位的CRC匹配队列的I-CRC和对照，并检索他们存档的石蜡包埋肿瘤样本。特异性识别染色体8、11和17的臂间区的FISH染色体计数探针首先用于细胞系，然后用于CRC组织微阵列以检测异染色体，然后用于计算CIN评分（CS）。对照CRC的第15百分位CS用于定义CIN表型。对照CRC和I-CRC的平均CS相似; 82%的I-CRC表现出CIN表型，与对照CRC相似。这项研究表明，CIN是I-CRC中基因组不稳定性的最常见因素。进一步的研究应评估CIN和微卫星不稳定性（MSI）在同一队列的I-CRC证实我们的研究结果，并进一步评估CIN和MSI的共同贡献I-CRC。
A substantial proportion of colorectal cancers (CRCs) are interval CRCs (I-CRCs; i.e., CRCs diagnosed soon after a colonoscopy). Chromosomal instability (CIN) is defined as an increase in the rate of which whole chromosomes/large chromosomal fragments are gained or lost and is observed in 85% of non-hereditary CRCs. The contribution of CIN to the etiology of I-CRCs remains unknown. We established a fluorescence in situ hybridization (FISH) approach to characterize CIN by enumerating specific chromosomes and determined the prevalence of numerical CIN in a population-based cohort of I-CRCs and control (sporadic) CRCs. Using the population-based Manitoba Health administrative databases and Manitoba Cancer Registry, we identified an age, sex, and colonic site of CRC matched cohort of I-CRCs and controls and retrieved their archived paraffin-embedded tumor samples. FISH chromosome enumeration probes specifically recognizing the pericentric regions of chromosomes 8, 11, and 17 were first used on cell lines and then CRC tissue microarrays to detect aneusomy, which was then used to calculate a CIN score (CS). The 15th percentile CS for control CRC was used to define CIN phenotype. Mean CSs were similar in the control CRCs and I-CRCs; 82% of I-CRCs exhibited a CIN phenotype, which was similar to that in the control CRCs. This study suggests that CIN is the most prevalent contributor to genomic instability in I-CRCs. Further studies should evaluate CIN and microsatellite instability (MSI) in the same cohort of I-CRCs to corroborate our findings and to further assess concomitant contribution of CIN and MSI to I-CRCs.
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DOI：
10.1056/nejmoa1301969
发表时间：
2013-09-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Nishihara R;Wu K;Lochhead P;Morikawa T;Liao X;Qian ZR;Inamura K;Kim SA;Kuchiba A;Yamauchi M;Imamura Y;Willett WC;Rosner BA;Fuchs CS;Giovannucci E;Ogino S;Chan AT
通讯作者：
Chan AT
影响因子：
7.5
作者：
Furlan, Daniela;Carnevali, Ileana W.;Carlo, Capella
通讯作者：
Carlo, Capella
影响因子：
4.3
作者：
Bishehsari, Faraz;Mahdavinia, Mahboobeh;Mariani-Costantini, Renato
通讯作者：
Mariani-Costantini, Renato
影响因子：
78.5
作者：
Issa, JP
通讯作者：
Issa, JP
影响因子：
9.3
作者：
Leaper, M;Johnston, MJ;Frizelle, FA
通讯作者：
Frizelle, FA