Germline mutation screening of the STK11/LKB1 gene in familial breast cancer with LOH on 19p

The recently cloned STK11/LKB1 on chromosome 19p has been shown to be a new tumor suppressor gene. Mutations in the LKB1/STK11 gene on chromosome 19p account for most cases of Peutz-Jeghers syndrome (PJS), in which intestinal hamartomas are associated with elevated risks of several cancer types, including breast cancer. A previous study revealed that familial breast cancer is associated with loss of heterozygosity (LOH) on 19p. To establish whether germline mutations of STK11/LKB1 account for familial breast cancer, 22 patients from 14 breast cancer families with LOH on 19p and one PJS family were selected for screening for germline mutations of LKB1/STK11. A combination of polymerase chain reaction (PCR)-heteroduplex, single-strand conformational polymorphism (SSCP) analyses, Southern blot analysis and direct sequencing were used for mutation detection. No mutations were identified. Germline mutations of LKB1/STK11 did not contribute to breast cancer in these families.     

少突胶质细胞肿瘤染色体1p、19q和10q杂合性缺失与临床预后的关系

目的 探讨少突胶质细胞肿瘤微卫星变异的遗传和分子特性及其与临床预后的关系。方法 26例少突胶质细胞瘤和25例伴有少突胶质细胞瘤成分的胶质母细胞瘤成对的血和肿瘤标本DNA提取后,进行微卫星不稳定性分析染色体1、19q和10q杂合性缺失。结果 54％少突胶质细胞瘤检出1pLOH,58％检出19qLOH,35％检出10q LOH,其中50％间变性少突胶质细胞瘤出现10q LOH。1p／19q LOH相伴存,二者密切相关（P〈0．0001）;40％GBMO检出1pLOH,仅4例1p LOH伴10q LOH;60％检出19q LOH,64％检出10q LOH。结论 1P和19q LOH是少突胶质细胞瘤分子和遗传特性之一,并且与化疗敏感和预后好有关,10qLOH是少突胶质细胞瘤进展标志。1PLOH与长PFS有关,10qLOH与短PFS有关。GBMO分子表型不同于GBM。