A comparison of CDKN2A mutation detection within the Melanoma Genetics Consortium (GenoMEL)

CDKN2A is the major melanoma susceptibility gene so far identified, but only 40% of three or more case families have identified mutations. A comparison of mutation detection rates was carried out by “blind” exchange of samples across GenoMEL, the Melanoma Genetics Consortium, to establish the false negative detection rates. Denaturing high performance liquid chromatography (DHPLC) screening results from 451 samples were compared to screening data from nine research groups in which the initial mutation screen had been done predominantly by sequencing. Three samples with mutations identified at the local centres were not detected by the DHPLC screen. No additional mutations were detected by DHPLC. Mutation detection across groups within GenoMEL is carried out to a consistently high standard. The relatively low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes.     

Smoking and risk of breast cancer in carriers of mutations in <Emphasis Type="Italic">BRCA1</Emphasis> or <Emphasis Type="Italic">BRCA2</Emphasis> aged less than 50 years

Background Cigarette smoke contains compounds that may damage DNA, and the repair of damage may be impaired in women with germline mutations in BRCA1 or BRCA2. However, the effect of cigarette smoking on breast cancer risk in mutation carriers is the subject of conflicting reports. We have examined the relation between smoking and breast cancer risk in non-Hispanic white women under the age of 50 years who carry a deleterious mutation in BRCA1 or BRCA2. Methods We conducted a case-control study using data from carriers of mutations in BRCA1 (195 cases and 302 controls) and BRCA2 (128 cases and 179 controls). Personal information, including smoking history, was collected using a common structured questionnaire by eight recruitment sites in four countries. Odds-ratios (OR) for breast cancer risk according to smoking were adjusted for age, family history, parity, alcohol use, and recruitment site. Results Compared to non-smokers, the OR for risk of breast cancer for women with five or more pack-years of smoking was 2.3 (95% confidence interval 1.6–3.5) for BRCA1 carriers and 2.6 (1.8–3.9) for BRCA2 carriers. Risk increased 7% per pack-year (p < 0.001) in both groups. Conclusions These results indicate that smoking is associated with increased risk of breast cancer before age 50 years in BRCA1 and BRCA2 mutation carriers. If confirmed, they provide a practical way for carriers to reduce their risks. Previous studies in prevalent mutation carriers have not shown smoking to increase risk of breast cancer, but are subject to bias, because smoking decreases survival after breast cancer. Northern California Family Registry for Breast Cancer: AS Whittemore, Stanford University School of Medicine, EM John, Northern California Cancer Center, A Felberg, Stanford University School of Medicine, V McGuire, Stanford University School of Medicine, DW West, Northern California Cancer Center, A Miron, Dana-Farber Cancer Institute, Harvard Medical School, DC Thomas, USC Keck School of Medicine, R Haile, USC Keck School of Medicine and Norris Comprehensive Cancer. Fox Chase Familial Breast Cancer Registry: M Daly, Fox Chase Cancer Center, A Godwin, Fox Chase Cancer Center, E Ross, Fox Chase Cancer Center. Coriell Institute: J Beck. New York Familial Breast Cancer Registry: MB Terry, Joseph L. Mailman School of Public Health, Columbia University. Utah Breast Cancer Family Registry: SS Buys, Huntsman Cancer Institute, V Venne, Huntsman Cancer Institute. Australian Breast Cancer Family Study: JL Hopper, The University of Melbourne, GG Giles, The Cancer Council Victoria, MRE McCredie, University of Otago, New Zealand, RL Milne, Spanish National Cancer Centre, MC Southey, The University of Melbourne, MA Jenkins, The University of Melbourne, C Apicella, The University of Melbourne. Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab), Peter MacCallum Cancer Centre. Ontario Familial Breast Cancer Registry: I Andrulis, Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, NF Boyd, Ontario Cancer Institute, J Knight, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, H Ozcelik, Samuel Lunenfeld Research Institute, Mount Sinai Hospital. Correspondence to: Dr NF Boyd, Campbell Family Institute for Breast Cancer Research, Room 10-415, Ontario Cancer Institute, 610 University Ave., Toronto, Ontario, Canada M5G 2M9. Boyd@uhnres.utoronto.ca     

ACOG Committee Opinion. Number 364 May 2007. Patents, medicine, and the interests of patients

Many basic scientists and clinicians support the right to obtain and enforce patents on drugs, diagnostic tests, medical devices, and most recently, genes. Although those who develop useful drugs, diagnostic and screening tests, and medical technologies have the right to expect a fair return for their efforts and risks, current interpretations of patent law have the potential to impede rather than promote scientific and medical advances. Policies regarding the patenting of scientific inventions, discoveries, and improvements must balance the need for the open exchange and use of information with the need ot make the pursuit of such knowledge financially rewarding.     

High incidence of chromosomal abnormalities in oocyte donors

Oocyte donors are chosen among phenotypically normal and fertile women who are not expected to carry any chromosomal abnormality. A high incidence of balanced structural chromosomal rearrangements has been found within oocyte donors. This result raises the question of a possible bias in their recruitment with respect to their familial background and/or personal reproductive history.     

胎儿组织int—2,Ki—ras和c—myc原癌基因的Southern blot杂交分析

本文用int-2、v-ki-ras和c-myc三种癌基因探针和核酸分子杂交技术,对6例胎儿(20或23周)的五种组织共21个DNA标本进行了Southern blot分析。实验结果表明,3例胚胎的10个DNA标本的int-2位点呈现BamHI多态性片段,ki-ras基因无扩增或重排。1例胚胎肾组织出现1条扩增的5.1kb c-myc杂交片段。上述结果有助于进一步研究胚胎组织中原癌基因的表达状态和肿瘤组织分化发育之间的潜在关系。     

人精子表面蛋白P34H重组表达载体的构建及诱导表达

目的 :获得纯化的人精子表面蛋白P34H用于基础和临床研究。　方法 :在克隆到P34H基因编码区全长的基础上 ,将P34H基因亚克隆至原核表达载体pQE 30中 ,构建重组表达载体pQE 30 /P34H。将pQE 30 /P34H转化至大肠埃希菌后 ,用异丙基 β D 硫代半乳糖苷 (IPTG)诱导表达 ,通过Ni NTA树脂进行亲和层析纯化上清中可溶性形式的重组蛋白P34H。对表达纯化重组蛋白的质粒进行DNA测序 ,并对重组蛋白P34H行十二烷基硫酸钠 聚丙烯酰胺凝胶电泳 (SDS PAGE)分析 ,鉴定其是否为所需目的蛋白。　结果 :经PCR和双酶切鉴定 ,重组表达载体pQE 30 /P34H为正确克隆。SDS PAGE和DNA测序证实 ,所获的重组蛋白确系所需目的蛋白。　结论 :用上述原核表达的方法可获得纯化的人精子表面蛋白P34H。