It is uncertain whether uterine leiomyosarcoma arises de novo or in preexisting leiomyoma. Leiomyoma-like areas can be seen associated with uterine leiomyosarcoma, raising the possibility of precursor lesions for uterine leiomyosarcoma. In this study, we examined cases of uterine leiomyosarcoma associated with leiomyoma-like areas at the histological, immunohistochemical and DNA level to further evaluate if benignlooking leiomyoma-like and uterine leiomyosarcoma areas are related. Cases of uterine leiomyosarcoma observed at the New York University Medical Center from 1994 to 2007 were reviewed for the presence of leiomyoma-like areas. Of the 26 cases of uterine leiomyosarcoma observed during this period, 18 cases had an associated leiomyoma-like area (five cellular leiomyoma, four symplastic leiomyoma, four cellular and symplastic leiomyoma and five usual type leiomyoma). Sixteen of the 18 cases were examined immunohistochemically for Ki-67, for estrogen receptor, progesterone receptor and for p53. Immunohistochemical profiles were as expected for leiomyoma-like (the mean expression of p53, ER, PR and Ki-67 at 0.3, 63, 75 and 0.6%, respectively), symplastic leiomyoma-like areas (the mean expression of p53, ER, PR and Ki-67 at 0.6, 85, 89 and 5.5%, respectively) and uterine leiomyosarcoma areas (the mean expression of p53, ER, PR and Ki-67 at 52, 38, 39 and 61%, respectively). In six cases, the leiomyoma-like and uterine leiomyosarcoma areas from each case were examined using high-density oligonucleotide array-CGH to determine genetic aberrations in the two areas. Nearly all the genetic aberrations found in leiomyoma-like areas were also found in the corresponding uterine leiomyosarcoma areas. In addition, uterine leiomyosarcoma areas had additional genetic aberrations. The immunohistochemical profiles and genetic aberrations of the examined cases suggest that uterine leiomyosarcoma could arise from the preexisting leiomyoma-like areas that often have a symplastic or cellular morphology.

Meiotic reciprocal recombination (crossing over) was examined in the outermost 60-80 kb of almost all Saccharomyces cerevisiae chromosomes. These sequences included both repetitive gene-poor subtelomeric heterochromatin-like regions and their adjacent unique gene-rich euchromatin-like regions. Subtelomeric sequences underwent very little crossing over, exhibiting approximately two-to threefold fewer crossovers per kilobase of DNA than the genomic average. Surprisingly, the adjacent euchromatic regions underwent crossing over at twice the average genomic rate and contained at least nine new recombination ''hot spots.'' These results prompted an analysis of existing genetic mapping data, which showed that meiotic reciprocal recombination rates were on average greater near chromosome ends exclusive of the subtelomeres. Thus, the distribution of crossovers in S. cerevisiae appears to resemble that found in several higher eukaryotes where the outermost chromosomal regions show increased crossing over.

Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty-seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array-based comparative genomic hybridization (array-CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 x 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an approximately 3-Mb (chr 8: 143,211,215-qter) duplication on 8q24.3-qter and a 4.4-Mb deletion on the 22q13.3-qter (chr 22: 45,047,068-qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240-kb (chr 6: 26,139,810-26,380,787) duplication and a 1.9-Mb deletion (chr 6: 26,085,971-27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array-CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array-CGH analysis may be beneficial during the investigations after sudden infant death.

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