Factors in decision making following genetic counseling for pre-natal diagnosis of de novo chromosomal rearrangements

A retrospective survey of genetic counselors was conducted in order to identify practice patterns and factors that influence a patient's decision making when a de novo translocation is diagnosed pre-natally. Different variables that influence patients' decisions about pregnancy management were assessed and compared. Specifically, the type of rearrangement and/or knowledge of the breakpoints, risks provided for abnormal outcome, anxiety, fetal ultrasound findings and personal reasons for parental decisions were evaluated. Our findings suggest that patient anxiety level significantly predicts pregnancy management decisions. This information may be of benefit in identifying potential areas of education for genetic counselors as well as other health care providers.     

Balanced reciprocal translocations: risk factors for aneuploid segregant viability

Reciprocal translocations were studied in two groups of balanced carrier couples: 202 had 210 translocation aneuploid between (LB) infants, and 95 couples had repetitive abortions (AB) without liveborn aneuploids. The observed translocation aneuploidies in the LB group were compared to predicted potential aneuploidies in AB by frequency of chromosome involvement, meiotic segregation mode, and mean trisomic, monosomic and combined genomic imbalances. Qualitative and quantitative differences identified genomic regions and chromosomes possibly vital for in utero survivability. LB aneuploidies indicate non-random chromosome involvement, selection of least detrimental segregants and segments, and predominant transmission from maternal balanced carriers (especially in 3:1 tertiary segregation, 93.5%). For an individual with a balanced reciprocal translocation and untested reproductive capability, an approach is given for predicting whether a translocation aneuploid conceptus will be liveborn or aborted.     

Increased frequency of female partner chromosomal abnormalities in patients with high-order implantation failure after in vitro fertilization

OBJECTIVE: To find the type and frequency of chromosomal abnormalities in a selected group of high-order implantation failure (> or =6 IVF trials and > or =15 transferred embryos) and to evaluate its impact on pregnancy outcome.DESIGN: A retrospective study.SETTING: In vitro fertilization (IVF) unit in a university affiliated hospital.PATIENT(S): Sixty-five couples with high-order implantation failure in IVF and embryo transfer.INTERVENTION(S): In vitro fertilization/embryo transfer (ET), work-up for implantation failure, cytogenetic analysis of the couple.MAIN OUTCOME MEASURE(S): We studied the type and frequency of chromosomal changes, quality of embryos, cumulative pregnancy rates, and pregnancy outcome.RESULT(S): The mean number of treatment cycles per patient, before karyotyping was 7.8 +/- 2.4 (range: 6 to 16 cycles). The mean cumulative number of all transferred embryos per patient was 25.7 +/- 10.3 (range: 9 to 65 embryos). Chromosomal abnormalities were found in 10 of 65 (15.4%) cases: translocations in six, mosaicism in two, and inversion or deletion in another two. The morphologic characteristics of the transferred embryos and the cumulative pregnancy rates were similar in patients with implantation failure with and without chromosomal changes. Three of the 16 patients with abnormal karyotype delivered and three miscarried within a follow-up period of 1 year.CONCLUSION(S): A high frequency of chromosomal aberrations was found in a selected group of high-order implantation failures, a similar frequency to recurrent miscarriages. Karyotyping is recommended as part of the work-up for repeated implantation failure in assisted reproduction. Treatment options include further IVF trials, preimplantation genetic diagnosis, or oocyte donation, tailored according to the type of chromosomal change. An international registry should be considered to assist in counseling these patients.     

Novel constitutional translocations t(3;5)(p25;q22) and t(1;14)(p31;q21) in patients with acute leukemia

Certain constitutional translocations have been described to be associated with an increased risk of malignant diseases. We report here two patients, one with acute myeloid leukemia (AML) and another with biphenotypic acute leukemia, in whom constitutional translocations t(3;5)(p25;q22) and t(1;14)(p31;q21) were observed, respectively. To our knowledge, none of the above translocations has been previously reported.     

Molecular cytogenetic analysis of breast cancer cell lines

The extensive chromosome rearrangements of breast carcinomas must contribute to tumour development, but have been largely intractable to classical cytogenetic banding. We report here the analysis by 24-colour karyotyping and comparative genomic hybridization (CGH) of 19 breast carcinoma cell lines and one normal breast epithelial cell line, which provide model examples of karyotype patterns and translocations present in breast carcinomas. The CGH was compared with CGH of 106 primary breast cancers. The lines varied from perfectly diploid to highly aneuploid. Translocations were very varied and over 98% were unbalanced. The most frequent in the carcinomas were 8;11 in five lines; and 8;17, 1;4 and 1;10 in four lines. The most frequently involved chromosome was 8. Several lines showed complex multiply-translocated chromosomes. The very aneuploid karyotypes appeared to fall into two groups that evolved by different routes: one that steadily lost chromosomes and at one point doubled their entire karyotype; and another that steadily gained chromosomes, together with abnormalities. All karyotypes fell within the range seen in fresh material and CGH confirmed that the lines were broadly representative of fresh tumours. The karyotypes provide a resource for the cataloguing and analysis of translocations in these tumours, accessible at http://www.path.cam.ac.uk/ approximately pawefish.     

用染色体FISH方法检测暴露于不同环境诱变因素居民的吸烟效应

背景与目的:研究包括天然辐射等不同环境诱变因素地区居民的吸烟效应.材料与方法:外周血采自10名在北京居住超过40年的吸烟居民,通过使用便携式个人剂量计随身测量24 h所得的剂量估算累积辐射剂量,通过荧光原位杂交(FISH)方法对北京吸烟居民的外周血淋巴细胞进行染色体易位的分析,其结果与10名广东高天然本底辐射(高本底)地区吸烟居民,7名对照地区吸烟居民,以及北京、高本底地区和对照地区的20、15名和16名非吸烟居民的结果进行了比较.结果:北京、高本底地区和对照地区的吸烟居民染色体易位率为(10.6±3.1)‰、(11.1±3.6)‰和(13.4±3.4)‰,非吸烟居民的为(9.6 ±5.0)‰、(11.7 ±4.7)‰和(8.4±3.1)‰.对照地区的吸烟居民与非吸烟居民的染色体易位率差异有统计学意义(P＜0.05,Mann-Whitney U test),北京和高本底地区的吸烟和非吸烟居民的染色体易位率差异无统计学意义(P＞0.05).结论:外周血淋巴细胞染色体易位的吸烟效应似乎被北京地区的环境诱变因素或高本底地区高出对照地区的天然辐射所抑制.     

Sarcomas: genetics, signalling, and cellular origins. Part 2: TET-independent fusion proteins and receptor tyrosine kinase mutations

Although the mechanisms that underlie sarcoma development are still poorly understood, the identification of non-random chromosomal translocations and receptor tyrosine kinase mutations associated with defined sarcoma types has provided new insight into the pathogenesis of these tumours. In Part 1 of the review (J Pathol 2007;213:4-20), we addressed sarcomas that express fusion genes containing TET gene family products. Part 2 of the review summarizes our current understanding of the implications of fusion genes that do not contain TET family members in sarcoma development, as well as that of specific mutations in genes encoding receptor tyrosine kinases (RTKs). The final section will serve as a summary of both reviews and will attempt to provide a synthesis of some of the emerging principles of sarcomagenesis.