TRANSLOCATION-(6-10)(P21-Q22) IN UTERINE LEIOMYOMAS

A translocation between chromosomes 6 and 10 was observed in two uterine leiomyomas. Translocation (6;10) may be important in the pathogenesis of a subgroup of uterine leiomyomas

Association of MYCN amplification and 1p deletion in neuroblastomas with high tumor vascularity

The biologic behavior of neuroblastoma (NB) is extremely variable; therefore, the clinical behavior may be reliably predicted based on the analysis of a panel of prognostic parameters. High vascular density has been correlated with aggressive tumor progression in many types of cancers. The goal of this study was to correlate the tumor vascularity in NB with status of MYCN and the short arm of chromosome 1 (1p) to address the association between angiogenesis and genetic markers of prognostic significance. The study population consisted of 33 patients with histologically proven diagnosis of primary NB and no history of previous chemotherapy. Histologic quantitation of tumor angiogenesis was performed using 3 different methods: microvessel density, vascular grading, and Chalkley counting. MYCN amplification and lp deletion were determined by using fluorescence in situ hybridization technique. The differentiation and mitosis-karyorrhexis index of tumor cells were also assessed using the Shimada System. MYCN amplification was present in 12 cases (36.3%), and lp deletion in 16 (48.5%). Both genetic changes significantly correlated with increased tumor vascularity. In addition, tumor vascularity was significantly increased in tumors with high mitosis-karyorrhexis index or of undifferentiated histology. We conclude that angiogenesis shows close association with histologic and genetic prognosticators in NB. Our data support the validity of recent applications of antiangiogenic agents which interfere or block NB progression

DNA copy number changes detected by comparative genomic hybridization and their association with clinicopathologic parameters in breast tumors

The purpose of this study was to use comparative genomic hybridization (CGH) to screen breast tumors for copy number changes: 22 ductal, 9 lobular, 7 mixed, 2 micropapillary carcinomas, and 2 ductal carcinoma in situ were studied and various regional genomic imbalances were detected. The majority of the aberrations identified in this study were in line with previous CGH findings. The most frequent DNA sequence copy number changes were 1q, 8q, and 20q gains. The frequency of 16q losses was significantly higher in lobular carcinomas. The nodal involvement was 10 times higher in cases showing losses of 13q than in cases having normal peak profile at this region. Estrogen receptor positivity was significantly higher in cases displaying 20q gains and 16q losses. Unambiguous high-level DNA amplifications have also been detected. These mapped to 4q31, 6q21-q22, 8q21-q24, 8p11.2similar top12, 11q13, 15q24similar toqter, 20q13.1similar toqter, and 20q12similar toqter chromosomal locations. Our results highlight several chromosomal regions that may be important in the molecular genetics of distinct clinicopathologic breast cancer subgroups. (C) 2003 Elsevier Inc. All rights reserved

Correlation of modified Shimada classification with MYCN and 1p36 status detected by fluorescence in situ hybridization in neuroblastoma

Neuroblastoma (NB) is a childhood cancer derived from neural crest cells, with a highly variable clinical course and biologic behavior. NB cells harbor complex genetic changes. Also, MYCN amplification is a well-known Molecular marker for aggressive progression, and deletion of the short arm of chromosome I is frequently observed in NB. The aim of this study was to investigate the correlation between genetic markers and prognostic morphological parameters to address the biology and underlying the clinical complexity of NB. Therefore, we perforated fluorescence in Situ hybridization analyses of chromosome band 1p36 and MYCN in a series of tumors from 43 cases classified according to the recommendation of International Neuroblastoma pathology Committee (modification of Shimada classification). The correlations of MYCN amplification status and two distinct types of 1p36 alterations (deletion and imbalance) with Shimada classification and histologic prognostic factors were statistically analyzed. Amplification of MYCN and 1p36 deletion was present in 14 (32.6%) and 18 (41.9%) cases, respectively. Sixteen cases (37.2%) displayed a favorable histology, while 27 (62.8%) had an unfavorable histology. The lp36 deletion was found to be an independent predictor Of Unfavorable histology by multivariate analysis (logistic regression test, P = 0.03), but the 1p36 imbalance did not show any significance. Both lp36 deletion and MYCN amplification showed significant correlation With Undifferentiated tumors (chi-square test, P = 0.002 and 0.03, respectively). Highly significant correlation was found between the higher mitotic karyorrhectic index (MKI) and MYCN amplification (chi-square test, P 0.05). We conclude that 1p36 deletion may be a reliable parameter in determining unfavorable histology and predicting prognosis in NB. Further Studies with prognostic data are needed to highlight its clinical significance. (c) 2007 Elsevier Inc. All rights reserved

Molecular analysis of chromosome 7q21.3 in uterine leiomyoma: Analysis using markers with linkage to insulin resistance

Recent sibling-pair linkage analyses have indicated possible linkage of noninsulin dependent diabetes mellitus (NIDDM) with a number of markers on the long arm of chromosome 7. A coincidental and recent discovery is that specific genetic anomalies identified on chromosome 7 in uterine leiomyoma tumor cells in many cases correspond, cytogenetically, to the same region where genetic linkage to insulin resistance has been identified. In the present study 15 closely spaced microsatellite markers were used to finely map deletion breakpoints and to test for allelic loss of 7q markers in 12 uterine leiomyoma tumor samples with cytogenetically defined deletions. Of the 9 informative tumor samples, three exhibited breakpoints in the same region where genetic linkage to insulin resistance has been identified (between PON and UT901). Because breakpoints in neoplasias often occur within or adjacent to expressed sequences, these breakpoints may provide a molecular tool to aid in the identification of candidate genes for insulin resistance. (C) Elsevier Science Inc., 1998

DELETION-6Q IN 3 CASES OF MIXED-TYPE LIPOSARCOMA IN ADDITION TO T(12-16)(Q13-P11)

We report the cytogenetic findings in three mixed liposarcoma following short-term cultures. During the course of cytogenetic investigation of various types of liposarcomas, we observed an interstitial deletion of the long arm of chromosome 6 together with the translocation (12;16) (q13;p11) in three tumors. Translocation (12;16) is associated with myxoid and mixed (myxoid/round cell) liposarcomas, although deletion of chromosome 6 has been observed in only a few of these tumors. Our findings suggest that del(6), as an additional change in myxoid liposarcoma, is probably related to tumor progression

CYTOGENETIC FINDINGS IN 21 MALIGNANT MELANOMAS

Cytogenetic analysis was performed on 21 tumor samples of malignant melanoma to identify the presence of consistent chromosome abnormalities. Four cases had a normal karyotype, and 17 were cytogenetically abnormal. Numerical chromosome alterations were observed in 15 tumors: 12 were hyperdiploid and three were hypodiploid. The most frequent losses consisted of chromosomes 5, 9, 17 and Y. The structural abnormalities were usually complex, consisting mainly of nonreciprocal translocations and deletions affecting 1p, 1q, 3p, and 9p. This study adds further data to previously reported melanoma cases, confirming that chromosomes 1, 3, 6, and 9 are nonrandomly affected