Allelic deletion mapping on chromosome 6q and X chromosome inactivation clonality patterns in cervical intraepithelial neoplasia and invasive carcinoma
Allelic deletion mapping on chromosome 6q and X chromosome inactivation clonality patterns in cervical intraepithelial neoplasia and invasive carcinoma
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DOI：
10.1006/gyno.2000.6087
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发表时间：
2001-03-01
影响因子：
4.7
通讯作者：
Emmert-Buck, M
中科院分区：
文献类型：
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作者：
Chuaqui, R;Silva, M;Emmert-Buck, M
Objective.分析42例宫颈上皮内瘤样病变（CIN 1、CIN 2、CIN 3）和22例浸润性宫颈癌患者的杂合性丢失（洛）和X染色体失活模式。利用激光捕获显微切割从每个病例中获得纯匹配的正常细胞和病变细胞。在6 q21-q25.1、8 p21、13 q12.3-q13和17 q12-q21四条染色体臂上扩增16个微卫星标记用于洛，以及HUMARA位点用于X染色体失活分析。在所有显示6号染色体长臂上存在洛缺失的病例中使用了8个额外的标记，其中进一步的组织材料可用于显微解剖。55%的癌症显示染色体带6 q21-q25.1缺失，43%在13q12.3-q13，40%在17 q12-q21。在CIN 3（40%）、CIN 2（37%）和CIN 1（10%）中鉴定出6 q上的缺失，在CIN 3（33%）和CIN 2（33%）中鉴定出13 q上的缺失，并且在染色体臂17 q上很少。进一步的6 q定位显示，标记D 6S 310（q22）代表缺失的着丝粒区，标记D 6S 255（q25-q16）代表缺失的端粒区。还鉴定了标记D 6S 281（q27）处的第二端粒缺失区。12/13例癌、13/14例CIN 3、5/10例CIN 2和0/6例CIN 1中检出单克隆X染色体失活模式。在宫颈肿瘤中发现了染色体6 q上的两个缺失区域，提示肿瘤抑制基因在此瘤变中失活。在颈部肿瘤进展的早期发现了该臂的洛缺失。13 q和17 q上的洛缺失在宫颈癌中也有发生。X染色体失活模式表明CIN在从CIN 1进展到CIN 3的过程中发展为单克隆病变。(C)北京：科学出版社.
Objective. Loss of heterozygosity (LOH) profiles and X chromosome inactivation patterns are analyzed in 42 patients with cervical intraepithelial neoplasias (CIN), including low-grade (CIN1) and high-grade (CIN2, CIN3) lesions, and 22 patients with invasive cervical carcinomas.Method. Laser capture microdissection was utilized to procure pure matched normal and lesional cells from each case. Sixteen microsatellite markers on four chromosomal arms, 6q21-q25.1, 8p21, 13q12.3-q13, and 17q12-q21, were amplified for LOH, as well as the HUMARA locus for X chromosome inactivation analysis. Eight additional markers spanning the long arm of chromosome 6 were utilized in all cases showing LOH on this arm and in which further tissue material was available for microdissection.Results. Fifty-five percent of carcinomas showed deletions on chromosome bands 6q21-q25.1, 43% on 13q12.3-q13, and 40% on 17q12-q21. Deletions on 6q were identified in CIN3 (40%), CIN2 (37%), and CIN1 (10%), on 13q in CIN3 (33%) and CIN2 (33%), and rarely on chromosomal arm 17q. Finer 6q mapping revealed that marker D6S310 (q22) represented the centromeric and marker D6S255 (q25-q16) the telomeric boundary of deletion. A second, telomeric area of deletion at marker D6S281 (q27) was also identified. Monoclonal X chromosome inactivation patterns were identified in 12/13 cancers, 13/14 CIN3, 5/10 CIN2, and 0/6 CIN1.Conclusions. Two areas of deletion on chromosome 6q were identified in cervical tumors, suggesting the presence of tumor suppressor gene(s) inactivated in this neoplasia. LOH on this arm were identified early during cervical tumor progression. LOH on 13q and 17q also occur in cervical cancers. X chromosome inactivation patterns suggest that CIN develops into a monoclonal lesion during progression from CIN1 to CIN3. (C) 2001 Academic Press.