Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome.
Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome.
复制标题
Peutz-Jeghers 综合征患者胃肠道息肉中 LKB1 和 β-catenin 基因的体细胞突变。
作者：
M. Miyaki;T. Iijima;T. Iijima;K. Hosono;R. Ishii;M. Yasuno;Takeo Mori;M. Toi;T. Hishima;N. Shitara;K. Tamura;K. Tamura;Joji Utsunomiya;N. Kobayashi;T. Kuroki;T. Iwama
Peutz-Jeghers综合征（PJS）的特征是多发性胃肠道错构瘤性息肉、粘膜皮肤黑色素沉积和癌症风险增加，主要发生在胃肠道。我们检测了9个PJS家族10例患者的27例胃肠道错构瘤性息肉中LKB 1、β-连环蛋白、APC、K-ras和p53基因的突变。在这些错构瘤性息肉中，1例肠息肉有腺瘤性病变，1例胃息肉有腺瘤性和癌性病变。在6个PJS家系中检测到LKB 1基因的生殖系突变。在5例息肉中发现LKB 1基因的体细胞突变，而在另外14例息肉中发现LKB 1基因19 p处的杂合性丢失（洛）。在错构瘤性息肉显微解剖的腺瘤性病变中，检测到β-连环蛋白突变和19 p洛缺失。此外，发现胃错构瘤性息肉中的癌性病变除了包含LKB 1位点的洛性缺失和β-连环蛋白突变外，还包含p53基因突变和p53位点的洛性缺失。K-ras基因突变在少数息肉中检出，而APC基因突变或5 q洛合性缺失在错构瘤性息肉中未检出。这些结果表明，PJS患者的胃肠道错构瘤性息肉是通过生殖系突变加上体细胞突变或未受影响的LKB 1等位基因的洛使LKB 1基因失活而发生的，β-连环蛋白基因和p53基因的额外突变将错构瘤性息肉转化为腺瘤性和癌性病变。
Peutz-Jeghers syndrome (PJS) is characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous melanin deposition, and increased risk of cancer, mainly in the gastrointestinal tract. We examined mutations of the LKB1, beta-catenin, APC, K-ras, and p53 genes in 27 gastrointestinal hamartomatous polyps from 10 patients in nine PJS families. Of these hamartomatous polyps, one intestinal polyp had an adenomatous lesion, and one gastric polyp contained adenomatous and carcinomatous lesions. Germ-line mutations of the LKB1 gene were detected in six PJS families. Somatic mutations of the LKB1 gene were found in 5 polyps, whereas loss of heterozygosity (LOH) at the LKB1 locus at 19p was seen in 14 other polyps. In adenomatous lesions microdissected from hamartomatous polyps, both beta-catenin mutation and 19p LOH were detected. Furthermore, a carcinomatous lesion in a gastric hamartomatous polyp was found to contain a mutation of the p53 gene and LOH at the p53 locus in addition to LOH at the LKB1 locus and a beta-catenin mutation. K-ras mutations were detected in a few polyps, whereas no APC mutation or 5q LOH was detected in hamartomatous polyps. These results suggest that gastrointestinal hamartomatous polyps in PJS patients develop through inactivation of the LKB1 gene by germ-line mutation plus somatic mutation or LOH of the unaffected LKB1 allele, and that additional mutations of the beta-catenin gene and p53 gene convert hamartomatous polyps into adenomatous and carcinomatous lesions.
影响因子：
11.2
作者：
S. Gruber;Mark M. Entius;G. Petersen;S. Laken;P. Longo;R. Boyer;A. Levin;U. Mujumdar;J. Trent;K. Kinzler;B. Vogelstein;S. Hamilton;M. Polymeropoulos;G. Offerhaus;F. Giardiello
通讯作者：
S. Gruber;Mark M. Entius;G. Petersen;S. Laken;P. Longo;R. Boyer;A. Levin;U. Mujumdar;J. Trent;K. Kinzler;B. Vogelstein;S. Hamilton;M. Polymeropoulos;G. Offerhaus;F. Giardiello
β-连环蛋白突变在小结直肠腺瘤中比在大腺瘤和浸润性癌中更常见。
DOI：
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发表时间：
1999
期刊：
Cancer research.
影响因子：
--
作者：
Samowitz,WS;Powers,MD;Spirio,LN;Nollet,F;vanRoy,F;Slattery,ML
通讯作者：
Slattery,ML