Tempest H G, Ko E, Chan P, Robaire B, Rademaker A, Martin R H
Department of Medical Genetics, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2 N 4N1.
Hum Reprod. 2008 Feb;23(2):251-8. doi: 10.1093/humrep/dem389. Epub 2007 Dec 14.
BACKGROUND Multicolour fluorescent in situ hybridization was utilized to detect sperm aneuploidy for chromosomes 13, 21, X and Y in testicular cancer and Hodgkin's lymphoma chemotherapy patients. METHODS Aneuploidy was assessed before, and 6, 12 and/or 18-24 months after, the initiation of chemotherapy, and compared with age matched controls. 635 396 sperm were scored blindly with 5000 sperm/patient/chromosome/ time point, where sperm was available. (First two phrases have been reversed). RESULTS Comparing testicular cancer and Hodgkin's lymphoma patients to each other and with controls, cancer-specific differences were identified. Hodgkin's lymphoma patients, particularly, exhibited significantly increased aneuploidy frequencies for all chromosomes throughout treatment. At 6 months, all cancer patients showed significantly increased frequencies of XY disomy and nullisomy for chromosomes 13 and 21. In general, aneuploidy frequencies declined to pretreatment levels 18 months after treatment initiation, but increased aneuploidy frequencies persisted in some chromosomes for up to 24 months. CONCLUSIONS Because of elevated aneuploidy frequencies prior to and up to 24 months from the start of chemotherapy, patients should receive genetic counselling about the potentially increased risk of an aneuploid conceptus from sperm cryopreserved prior to chemotherapy, and for conceptions up to 2 years after the initiation of treatment.
采用多色荧光原位杂交技术检测睾丸癌和霍奇金淋巴瘤化疗患者精子中13、21、X和Y染色体的非整倍体情况。方法:在化疗开始前、化疗开始后6、12和/或18 - 24个月评估非整倍体情况,并与年龄匹配的对照组进行比较。在有精子样本的情况下,对635396条精子进行盲法评分,每个患者、每条染色体、每个时间点评分5000条精子。结果:比较睾丸癌和霍奇金淋巴瘤患者之间以及与对照组的情况,发现了癌症特异性差异。特别是霍奇金淋巴瘤患者在整个治疗过程中所有染色体的非整倍体频率均显著增加。在6个月时,所有癌症患者13号和21号染色体的XY二体和缺体频率均显著增加。总体而言,非整倍体频率在治疗开始18个月后降至预处理水平,但某些染色体的非整倍体频率增加持续长达24个月。结论:由于化疗开始前及开始后长达24个月非整倍体频率升高,患者应接受遗传咨询,了解化疗前冷冻保存的精子以及治疗开始后长达2年受孕产生非整倍体胚胎的潜在风险增加。