Loss of heterozygosity on chromosome arms 3p and 6q in microdissected adenocarcinomas of the uterine cervix and adenocarcinoma in situ
Loss of heterozygosity on chromosome arms 3p and 6q in microdissected adenocarcinomas of the uterine cervix and adenocarcinoma in situ
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DOI：
10.1002/cncr.10275
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发表时间：
2002-02-01
期刊：
影响因子：
6.2
通讯作者：
Chuaqui, RF
中科院分区：
文献类型：
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作者：
Acevedo, CM;Henríquez, M;Chuaqui, RF
背景尽管子宫颈腺癌的发生率越来越高，但关于这种肿瘤类型中肿瘤抑制基因（TSGs）的失活知之甚少。作者分析了40例宫颈腺癌中36例伴腺分化癌和5例原位腺癌的杂合性丢失（洛）。作者使用激光捕获显微切割从档案材料和DNA中分析了样品，这些DNA在以下位点上用微卫星标记扩增：3p14.2（D3S1234，D3S1300），3p21.3（D3S1029，D3S1447），3p22-24（D3S1537，D3S1351），6q21-23.3（D6S250），6q25.1（ESR），6q25.2（D6S255），8p21（D8S136，D8S1820），13q12.3（D13S220，D13S267），17q21（D17S579，D17S855）。在显示洛的病例中，研究了跨越3号染色体短臂的8个额外标记（3 p12-p25）和跨越6号染色体长臂的6个标记（6 q11-q27），以进一步确定缺失间隔。癌症中等位基因丢失的频率为染色体3 p：49%（p14.2：35%，p21.3：23%，p22-24：41%），6 q：48%（q21-23.1：39%，q25.1：45%，q25.2：7%），13 q：22%，17 q：6%和8 p：18%。在染色体臂3 p上，作者的数据表明至少有两个离散的缺失区域：标记D3 S1234（p12）和D3 S1766（p14.2-14.3）之间的近端区域，以及标记D3 S4623（p21.3）端粒的第二个远端间隔。在染色体6 q上，缺失区域在标记D 6S 300（q22）和D 6S 255（q25.2）之间。5例宫颈癌前病变中2例在染色体臂3 p处出现洛合性缺失，2例在染色体臂6 q处出现等位基因缺失，提示这些基因在宫颈癌发生的早期可能失活。作者已经确定了三个染色体区域，可能含有参与宫颈腺癌发展/进展的TSG，3 p12 -14.2，3p21.3-pter和6 q22 -25.2。在原位腺癌中也检测到缺失，表明这些基因可能在宫颈肿瘤发生的早期失活。癌症2002;94：793-802. (C)2002年美国癌症协会。
BACKGROUND. Despite the increasing frequency of adenocarcinomas of the uterine cervix, little is known regarding inactivation of tumor suppressor genes (TSGs) in this tumor type. The authors analyzed loss of heterozygosity (LOH) in 36 carcinomas of the cervix with glandular differentiation, and 5 adenocarcinoma in situ in 40 patients.METHODS. The authors analyzed samples using laser capture microdissection from archival material and DNA amplified with microsatellite markers on the following loci: 3p14.2 (D3S1234, D3S1300), 3p21.3 (D3S1029, D3S1447), 3p22-24 (D3S1537, D3S1351), 6q21-23.3 (D6S250), 6q25.1 (ESR), 6q25.2 (D6S255), 8p21 (D8S136, D8S1820), 13q12.3 (D13S220, D13S267), 17q21 (D17S579, D17S855). Eight additional markers spanning the short arm of chromosome 3 (3p12-p25) and six spanning the long arm of chromosome 6 (6q11-q27) were studied in the cases showing LOH to further define the deletion intervals.RESULTS. The frequency of allelic loss in cancers was chromosome 3p: 49% (p14.2: 35%, p21.3: 23%, p22-24:41%), 6q: 48% (q21-23.1:39%, q25.1:45%, q25.2:7%),13q: 22%, 17q: 6%, and 8p: 18%. On chromosome arm 3p, the authors' data suggest at least two discrete areas of deletion: a proximal area between markers D3S1234 (p12) and D3S1766 (p14.2-14.3), and a second distal interval, telomeric from marker D3S4623 (p21.3). On chromosome 6q, the deletion area is between marker D6S300 (q22) and D6S255 (q25.2). Two of five preneoplastic lesions showed LOH on chromosome arm 3p, and two five showed allelic loss on chromosome arm on 6q, suggesting the genes might be inactivated early in cervical tumorigenesis.CONCLUSIONS. The authors have identified three chromosomal regions that may harbor TSGs involved in the development/progression of adenocarcinomas of the uterine cervix, 3p12-14.2, 3p21.3-pter, and 6q22-25.2. Deletions also were detected in adenocarcinoma in situ, suggesting the genes may be inactivated early in cervical tumorigenesis. Cancer 2002;94:793-802. (C) 2002 American Cancer Society.