Tsou H C, Teng D H, Ping X L, Brancolini V, Davis T, Hu R, Xie X X, Gruener A C, Schrager C A, Christiano A M, Eng C, Steck P, Ott J, Tavtigian S V, Peacocke M
Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
Am J Hum Genet. 1997 Nov;61(5):1036-43. doi: 10.1086/301607.
Cowden syndrome (CS) is an autosomal dominant disorder associated with the development of hamartomas and benign tumors in a variety of tissues, including the skin, thyroid, breast, endometrium, and brain. It has been suggested that women with CS are at increased risk for breast cancer. A locus for CS was recently defined on chromosome 10 in 12 families, resulting in the identification of the CS critical interval, between the markers D10S215 and D10S541. More recently, affected individuals in four families with CS have been shown to have germ-line mutations in a gene known as "PTEN," or "MMAC1," which is located in the CS critical interval on chromosome 10. In this study, we report three novel MMAC1 mutations in CS and demonstrate that MMAC1 mutations are associated with CS and breast cancer. Furthermore, we also show that certain families and individuals with CS do not have mutations in the coding sequence of MMAC1. Finally, we did not detect MMAC1 mutations in a subpopulation of individuals with early-onset breast cancer, suggesting that germ-line mutations in this gene do not appear to be common in this group.
考登综合征（CS）是一种常染色体显性疾病，与多种组织（包括皮肤、甲状腺、乳腺、子宫内膜和脑）中错构瘤和良性肿瘤的发生有关。有人提出，患有CS的女性患乳腺癌的风险增加。最近在12个家族中确定了CS在10号染色体上的一个位点，从而确定了CS关键区间，位于标记D10S215和D10S541之间。最近，四个患有CS的家族中的患病个体已被证明在一个名为“PTEN”或“MMAC1”的基因中存在种系突变，该基因位于10号染色体的CS关键区间。在本研究中，我们报告了CS中三个新的MMAC1突变，并证明MMAC1突变与CS和乳腺癌相关。此外，我们还表明，某些患有CS的家族和个体在MMAC1编码序列中没有突变。最后，我们在早发性乳腺癌个体亚群中未检测到MMAC1突变，这表明该基因的种系突变在该组中似乎并不常见。
