Recurrent and multiple bladder tumors show conserved expression profiles

<p>Abstract</p> <p>Background</p> <p>Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors.</p> <p>Methods</p> <p>Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses.</p> <p>Results</p> <p>We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles.</p> <p>Conclusion</p> <p>Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors.</p

Formation of trisomies and their parental origin in hyperdiploid childhood acute lymphoblastic leukemia.

High hyperdiploidy, common in childhood acute lymphoblastic leukemia (ALL) with a favorable prognosis, is characterized by specific trisomies. Virtually nothing is known about its formation or pathogenetic impact. We evaluated 10 patients with ALL using 38 microsatellite markers mapped to 18 of the 24 human chromosomes to investigate the mechanisms underlying hyperdiploidy and to ascertain the parental origin of the trisomies. Based on the results, doubling of a near-haploid clone and polyploidization with subsequent losses of chromosomes could be excluded. The finding of equal allele dosage for tetrasomy 21 suggests that hyperdiploidy originates in a single aberrant mitosis, though a sequential gain of chromosomes other than 21 in consecutive cell divisions remains a possibility. Our study, the first to address experimentally the parental origin of trisomies in ALL, revealed no preferential duplication of maternally or paternally inherited copies of X, 4, 6, 9, 10, 17, 18, and 21. Trisomy 8 was of paternal origin in 4 of 4 patients (P = .125), and +14 was of maternal origin in 7 of 8 patients (P = .0703). Thus, the present results indicate that imprinting is not pathogenetically important in hyperdiploid childhood ALL, with the possible exception of the observed parental skewness of +8 and +14. (Blood. 2003;102:3010-3015) (C) 2003 by The American Society of Hematology

A) 1-Pearson correlation distances among 8 normal samples, metachronous samples from 7 patients, 62 unique Ta samples, and 19 unique T1 samples estimates from expression data obtained from the 25k cDNA platform

B) 1-Pearson correlation distances among 7 normal samples, meta- or synchronous tumors from 12 patients, and 36 unique T1 tumors estimated from expression data obtained from 36k oligonucleotide platform. The calculation of distances among meta- and synchronous is based on distances among tumors originating from the same patients.<p><b>Copyright information:</b></p><p>Taken from "Recurrent and multiple bladder tumors show conserved expression profiles"</p><p>http://www.biomedcentral.com/1471-2407/8/183</p><p>BMC Cancer 2008;8():183-183.</p><p>Published online 30 Jun 2008</p><p>PMCID:PMC2483988.</p><p></p

A) HCA of 15 metachronous tumors from 7 patients, 84 unique tumors, and 8 normal samples hybridized to the 25k cDNA array

B) HCA of 38 meta- or synchronous tumors from 17 patients, 91 unique tumors, and 7 normal samples hybridized to the 36k oligonucleotide array. Meta- and synchronous tumors from the same patients are colored the same.<p><b>Copyright information:</b></p><p>Taken from "Recurrent and multiple bladder tumors show conserved expression profiles"</p><p>http://www.biomedcentral.com/1471-2407/8/183</p><p>BMC Cancer 2008;8():183-183.</p><p>Published online 30 Jun 2008</p><p>PMCID:PMC2483988.</p><p></p