Differential loss of heterozygosity in the region of the Cowden locus within 10q22-23 in follicular thyroid adenomas and carcinomas.
Differential loss of heterozygosity in the region of the Cowden locus within 10q22-23 in follicular thyroid adenomas and carcinomas.
复制标题
滤泡性甲状腺腺瘤和癌中 10q22-23 内 Cowden 基因座区域的杂合性差异丢失。
作者：
Deborah J. Marsh;Zimu Zheng;Jan Zedenius;H. Kremer;G. Padberg;Catharina Larsson;Michel Longy;Charis Eng
考登病（一种常染色体显性遗传性癌症综合征）的易感基因最近被定位到染色体10q22-23亚带上标记D10S541和D10S564之间约6厘米的间隔。乳糜泻的特点是许多器官系统的错构瘤，包括甲状腺、乳房、皮肤和胃肠道，以及甲状腺癌和乳房癌。滤泡性甲状腺腺瘤和甲状腺癌是乳糜泻的重要组成部分；因此，我们试图检测其散发的对应肿瘤在考登临界区间内和两侧的20 cm区域微卫星标记的杂合性缺失（LOH）。总共分析了38例散发性甲状腺肿瘤。19例滤泡性甲状腺腺瘤中有5例（26%）和9例<s:1>甲状腺细胞腺瘤中有1例（11%）在CD间期出现LOH。此外，在这些合并LOH的腺瘤中，4 / 3（75%）为非典型滤泡性腺瘤，而15 / 2（13%）为典型滤泡性腺瘤。令人惊讶的是，在10个滤泡癌中，没有在该区域检测到LOH。重叠最短的区域包括标记D10S1735和D10S1739。如果在这些散发性肿瘤中观察到的LOH与CD基因有关，则可将Cowden临界区间修正为D10S579和D10S564定义的区间内。在这个狭窄的间隔中LOH暗示CD基因，或在这个间隔中的另一个基因，在滤泡性甲状腺肿瘤发生中。然而，这并不能解释滤泡性癌中LOH的缺乏。综上所述，这可能是反对非典型腺瘤逐步发展为癌的证据。另外，散发性甲状腺腺瘤的形成可能独立于该位点，但该区域的缺失可能阻止癌的形成，从而暗示CD基因可能是致癌基因或生长促进因子。
The susceptibility gene for Cowden disease (CD), an autosomal dominant inherited cancer syndrome, has recently been mapped to an approximately 6-cM interval on chromosome subband 10q22-23 between the markers D10S541 and D10S564. CD is characterized by hamartomas of many organ systems, including the thyroid, breast, skin, and gastrointestinal tract, as well as carcinoma of the thyroid and breast. Follicular thyroid adenomas and carcinomas are significant component tumors in CD; thus, we sought to examine their sporadic counterpart tumors for loss of heterozygosity (LOH) of microsatellite markers in the 20-cM region within and flanking the Cowden critical interval. In all, 38 sporadic thyroid tumors were analyzed. LOH within the CD interval was observed in 5 of 19 (26%) follicular thyroid adenomas and 1 of 9 (11%) Hürthle cell adenomas. Furthermore, of these adenomas with LOH, 3 of 4 (75%) were atypical follicular adenomas, whereas 2 of 15 (13%) were typical follicular adenomas. Surprisingly, no LOH was detected in this region in 10 follicular carcinomas. The shortest region of overlap includes the markers D10S1735 and D10S1739. If the LOH observed in these sporadic tumors is related to the CD gene, then the Cowden critical interval can be revised to lie within the interval defined by D10S579 and D10S564. LOH in this narrow interval implicates the CD gene, or another gene in that interval, in follicular thyroid tumorigenesis. However, this does not explain the lack of LOH in follicular carcinomas. Taken together, it may instead be evidence against a stepwise progression from atypical adenomas to carcinomas. Alternatively, sporadic thyroid adenoma formation may be independent of that locus, but loss of this region could prevent carcinoma formation, thus implying that the CD gene may be an oncogene or growth promoter.
通过代表性差异分析鉴定胰腺癌中位于 BRCA2 区域内的纯合缺失。
DOI：
10.1073/pnas.92.13.5950
发表时间：
1995
影响因子：
11.1
作者：
Schutte,M;daCosta,LT;Hahn,SA;Moskaluk,C;Hoque,AT;Rozenblum,E;Weinstein,CL;Bittner,M;Meltzer,PS;Trent,JM
通讯作者：
Trent,JM
DOI：
10.1210/jcem.79.5.7962323
发表时间：
1994-11
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
K. Zeki;D. Spambalg;Nazy Sharifi;R. Gonsky;J. Fagin
通讯作者：
K. Zeki;D. Spambalg;Nazy Sharifi;R. Gonsky;J. Fagin
人类甲状腺肿瘤的分子遗传学。
影响因子：
10.5
作者：
Fagin,JA
通讯作者：
Fagin,JA