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S Heim

Publications and source records attributed to S Heim.

At least 127 records · Page 7Linked to original sources
PubMed1995

Cytogenetic findings in uterine epithelioid leiomyomas.

Epithelioid leiomyomas of the uterus, unlike ordinary leiomyomas, show substantial epithelial differentiation. No chromosome abnormalities have been reported in uterine epithelioid leiomyomas before. We analyzed short-term cultures from five such tumors and detected abnormal karyotypes in four. A del(7) (q21.2q31.2) was found in two tumors, in one as the only change and in the other as a secondary aberration acquired during clonal evolution. Rearrangement of chromosomal band 12q15, another of the cytogenetic hallmarks of ordinary uterine leiomyomas, was seen in the form of a t(10;12) in one tumor. Band 17q21 was involved in structural aberrations in two cases. The data we present indicate that epithelioid leiomyomas are fundamentally similar cytogenetically, and hence presumably also pathogenetically, to the much more common smooth muscle-differentiated uterine myomas. The only differences hinted at are that epithelioid tumors may be karyotypically more complex and more often have rearrangements of 17q21.

Adult↗
PubMed1995

Near-diploid karyotypes with recurrent chromosome abnormalities characterize early-stage endometrial cancer.

Cytogenetic investigation was attempted on 15 endometrial tumors. Whenever possible, a combination of direct harvesting and short-term culture (with or without prior methotrexate synchronization) was used. The analysis was successful in 13 cases: 12 carcinomas of stage I and one atypical hyperplasia. Clonal abnormalities were found in 10 tumors, whereas the remaining three showed a normal karyotype. The modal chromosome number was near-diploid. The abnormal karyotypes contained relatively simple numerical or structural aberrations in all but one tumor, a serous papillary carcinoma with multiple complex changes as well as cytogenetic evidence of intratumor heterogeneity. Gain of 1q, trisomy for chromosomes 2, 7, 10 (this trisomy was shown by in situ hybridization to be present also in a large number of interphase cells), and 12, and loss of chromosome 22 were recurrent aberrations; these are also the cytogenetic anomalies that have been consistently associated with endometrial carcinomas in previous studies. The utilization of both direct harvesting and short-term culture in several cases increased the frequency with which abnormal karyotypes were found; sometimes aberrations were found by the first method but not by the other, and vice versa. Never were different clonal anomalies found by the two approaches in the same case. Synchronization of the cultures generally led to chromosome preparations with more mitoses and of better quality. Again, no different anomalies were found in synchronized and standard cultures from the same tumor.

Chromosome Aberrations↗
PubMed1995

Chromosome analysis of uterine adenomyosis. Detection of the leiomyoma-associated del(7q) in three cases.

Adenomyosis is a uterine disease whose defining characteristic is the presence deep in the myometrium of endometrial glands and stroma. The condition is believed to arise from inordinate downward growth by contiguity from the endometrium rather than from in situ metaplasia or neoplasia. No acquired chromosome abnormalities have been associated with adenomyosis before. We analyzed short-term cultures from three cases and detected in all of them a del(7) (q21.2q31.2), a karyotypic anomaly that has hitherto been found repeatedly only in uterine leiomyomas. The cytogenetic similarity to leiomyoma suggests that the del(7q) was present in the mesenchymal or, more precisely, smooth muscle cells of the adenomyosis lesions. The very fact that clonal chromosome abnormalities were present questions whether the prevailing understanding of adenomyosis pathogenesis is adequate; the cytogenetic data would better fit a model of the disease envisioning the intramyometrial endometrial foci as having arisen through a neoplastic process.

Adult↗
PubMed1995

Cytogenetic analysis of short-term cultured squamous cell carcinomas of the lung.

Cytogenetic analysis of 122 primary squamous cell carcinomas of the lung revealed clonal abnormalities in 56 tumors. Karyotypes with simple numerical changes were found in 32 tumors: 45,X,-Y in 28, 47,XY,+7/45,X-Y, in two, 47,XY,+Y/45,X,-Y and 47,XY,+20/45,X,-Y in one tumor each. A super-numerary ring chromosome was the sole anomaly in two tumors. Complex structural changes were found in 22 tumors. The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (15 tumors), 3, 7, and 11 (10 tumors each), 5 and 6 (nine tumors each), and 2, 8, and 12 (eight tumors each). The bands and regions most often affected were 1p11-13 and 5cen (six tumors each), 11p11, 14p11-13, 15cen, and 17p11-12 (five tumors each), and 12p13 and 13cen (four tumors each). The only recurrent changes were the whole-arm rearrangements i(5)(p10) (five tumors) and i(6)(p10), der(9;15)(q10;q10), and der(13;15)(q10;q10) (two tumors each). The most prominent genomic imbalances were, apart from losses of the Y chromosome, losses from 1p, 3p, 5q, 6q, 8p, 13p, and 14p and gains from 1q and 5p.

Aged↗
PubMed1995

Clonal karyotypic evolution in a pediatric neurofibrosarcoma.

A retroperitoneal neurofibrosarcoma infiltrating the spine of a 2-year-old boy was investigated cytogenetically three times over a 5-month period. The first sample, from a diagnostic fine-needle aspiration biopsy, had a supernumerary i(1)(q10) as the sole clonal aberration; two cells showed monosomy 18 in addition to the isochromosome. The second sample, obtained at tumor resection 3 weeks later, had the karyotype 47,XY, +i(1)(q10), -18, +21/45,XY, -18. After 5 months, a large local recurrence was resected. The chromosome analysis showed further clonal evolution: 45,XY, +1,der (1;11)dic(1;11)(q44;q13)i(1)(q10), inv(6)(p21q12), -17. The findings indicate that formation of i(1)(q10) and loss of chromosome 18 may be early genetic events in neurofibrosarcoma development.

Child, Preschool↗
PubMed1995

Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL).

Pancytopenia followed by a period of spontaneous recovery may precede the diagnosis of acute lymphoblastic leukemia (pre-ALL). Although both pre-ALL and myelodysplastic syndromes are preleukemic in a strictly temporal sense, there are several marked differences between the two conditions. We present eight children with pre-ALL who represented 2% of all cases of childhood ALL. The bone marrow was normo- or hypocellular with increased reticulin fibrosis during the pre-ALL phase. No cytogenetic abnormalities were found at the pre-ALL phase, but had developed at the time of overt leukemia in four of the six children examined. Based on the findings in our patients and on cases reported in the literature, we argue that pre-ALL is likely to represent a paraneoplastic syndrome early in the leukemic development that might be mediated via inhibitory properties related to clonally expanding but still cytogenetically normal cells. The findings may indicate a multistep pathogenesis of ALL.

Adolescent↗
PubMed1994

Karyotypic pattern of pancreatic adenocarcinomas correlates with survival and tumour grade.

The relationship between cytogenetic findings and clinicohistopathological parameters was assessed in 29 patients with pancreatic adenocarcinoma. Karyotypic analysis revealed normal karyotypes (N) in 8 carcinomas and abnormal karyotypes (A) in 21. Within the A group, 8 cases had simple chromosome abnormalities (As), i.e., only one numerical or structural aberration, whereas 13 had complex changes with multiple numerical and structural abnormalities (Ac). No significant differences between the N and A groups were detected in terms of tumour grade, clinical stage, type of surgery performed, tumour site or size or the patient's age and survival. A correlation analysis between groups As and Ac revealed a significant difference with regard to grade, poorly differentiated carcinomas being more frequent in the Ac group. Patients in the Ac group had also a significantly shorter survival time than those in the As group. None of the other potentially prognostic parameters, i.e., grade, tumour site, stage and type of surgery performed, correlated significantly with clinical outcome.

Adenocarcinoma↗
PubMed1994

Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage.

Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange or micronuclei in PBL. In order to standardize for the interlaboratory variation, the results were trichotomized for each laboratory into three strata: low (1-33 percentile), medium (34-66 percentile), or high (67-100 percentile). In this second follow-up, a total of 85 cancers were diagnosed during the observation period (1970-1991). There was no significant trend in the standardized incidence ratio with the frequencies of sister chromatid exchange or micronuclei, but the data for these parameters are still too limited to allow firm conclusions. There was a statistically significant linear trend (P = 0.0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk.

Adult↗
PubMed1994

Karyotypic characterization of bronchial large cell carcinomas.

Cytogenetic analysis of short-term cultures from 26 primary bronchial large cell carcinomas and 1 metastasis from a primary large cell carcinoma revealed clonal chromosome abnormalities in 20 tumors and a normal karyotype in 6. No outgrowth was obtained in 1 case. Simple aberrations were present in 3 tumors; in 1, the only change was a reciprocal translocation between chromosomes 1 and 6, in another the sole anomaly was a supernumerary marker ring chromosome and in a third loss of the Y chromosome was the only clonal change. The remaining 17 tumors had complex karyotypes. The chromosomes most frequently involved in structural rearrangements were chromosomes 1, 2, 3, 5, 6, 7, 8, 10, 11, 13, 14 and 17. The bands most frequently affected were 1q11-12, 1p13, 7q11, and 17p11-13. The rearrangements led to repeated losses of 1p, 1q, 3p, 6q, 7q and 17p and gains of 5q and 7p. The emerging karyotypic picture of large cell lung carcinomas indicates more similarities with adenocarcinomas than with other pathologic subgroups of lung cancer.

Aged↗
PubMed1994

Loss of chromosome band 8q24 in sporadic osteocartilaginous exostoses.

We have karyotyped eight sporadic osteocartilaginous exostoses (OCE), a tumor type not characterized cytogenetically before. Five tumors had only normal karyotypes, whereas three displayed the following abnormal karyotypes: 46,XY,del(8)(q24.1); 46,XX,del(8)(q22), t(8;14)(q24.1;q32); and 46,XY,der(8)t(1;8)(q21;q24),inv(12)(p11q13). All three aberrant cases thus had structural rearrangements leading to loss of the distal part of 8q. This is of particular interest because multiple OCE are part of the disease phenotype in patients with the autosomal dominant tricho-rhino-phalangeal syndrome type II (TRP II), many of whom have constitutional loss of genetic material from 8q24.1. We hypothesis that band 8q24.1 harbors a tumor suppressor gene, the homozygous inactivation of which is important in the genesis of both inherited and sporadic OCE. In the familial form, i.e., in TRP II, loss or functional inactivation of one allele is inherited and only the second mutation is due to a somatic event, whereas both mutations are somatic in the sporadic forms. This hypothesis can be tested by analysis of sporadic and inherited OCE for homozygous loss of 8q24 material with molecular genetic techniques.

Adolescent↗
PubMed1994

Clonal karyotypic abnormalities in colorectal adenomas: clues to the early genetic events in the adenoma-carcinoma sequence.

Cytogenetic analysis of short-term cultures from colorectal adenomas revealed acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only numerical changes were found, whereas 10 had structural rearrangements. Trisomy 7 was found as the sole change in one of the tumors and together with other numerical changes in another. A +7 was also present in one case with structural aberrations. Other recurrent numerical aberrations were -14 and -18, both found in 2 adenomas with structural karyotypic changes; in addition, one chromosome 14 was lost in one of the tumors with only numerical changes. The chromosome most often involved in structural aberrations was chromosome 1. In 6 cases, the rearrangements led to changes in 1p, always with loss of material. The breakpoints were at 1p32-36. One adenoma had deletion of 1p as the only change. Other chromosomes that were involved in changes in more than 2 cases were chromosomes 8, 13, and 17. These rearrangements typically led to gain of 8q and 13q and loss of 17p. The adenomas with structural abnormalities were generally larger and had a higher degree of dysplasia than did the adenomas with numerical changes only or those with a normal karyotype. All adenomas with a tubulovillous or villous architecture had structural rearrangements. Our findings confirm that a subset of colorectal adenomas exists that have only numerical chromosome aberrations. They also support our previous conclusion that loss of material from distal 1p is an early event in colorectal tumorigenesis, but that other cytogenetic aberrations follow and typically are present already at the adenomatous stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

Complex karyotypic abnormalities in a primary carcinoma of the fallopian tube.

Short-term cultures from a primary carcinoma of the Fallopian tube, a tumor type not characterized before by chromosome banding, were examined cytogenetically. Complex chromosome aberrations were found in all mitoses, yielding the karyotype 41,XX,del(1)(p34),del(2)(q31),i(8)(q10),-9, + dic(9;19)(p13;p13), der(12)t(9;12)(p13;q22),-13,-16,-17,-18,-19,-22, +r [61]/84-86,idemx2[15]. Several of the aberrations in the present case are similar to changes found in adenocarcinomas of other organs, including carcinomas of the ovaries and uterus, indicating pathogenetic similarities between Fallopian tube malignancies and the more common gynecologic cancers.

Adenocarcinoma, Papillary↗
PubMed1994

Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22).

It has been shown that the gene ERG in 21q22 is rearranged in the t(16;21)(p11;q22) associated with acute myeloid leukemia (AML). ERG is a member of the ETS gene family and is fused with EWS in a subset of Ewing's sarcomas. EWS in 22q12 has a very high homology with FUS (also called TLS) in 16p11; the latter gene is rearranged in the t(12;16)(q13;p11) that characterizes myxoid liposarcoma. To investigate whether FUS is involved in the t(16;21) of AML, we used the Southern blot technique and polymerase chain reaction (PCR) to examine the bone marrow of a 3-year-old boy with a t(16;21)(p11;q22)-positive AML. Hybridization of Southern blot filters containing digested DNA with probes for FUS and ERG showed both germline and aberrant fragments. Using specific primers for the 5' part of FUS and the 3' part of ERG, we amplified a 4.4 kb genomic FUS/ERG DNA fragment from the leukemic sample. In a second PCR experiment, in which we used primers upstream of the 5' part of ERG and downstream of the 3' part of FUS, a 5.6 kb fragment was amplified. Blotting and hybridization with specific probes for FUS and ERG revealed that the amplified fragments consisted of FUS/ERG and ERG/FUS hybrid DNA. Both PCR fragments, when used as probes, detected germline ERG and FUS as well as aberrant fragments on Southern blot filters. The results suggest that the t(16;21) in AML leads to rearrangement and fusion of the FUS and ERG genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Clonal structural chromosome aberrations in fibrous dysplasia.

Cytogenetic analysis of short-term cultures from a case of monostotic fibrous dysplasia in a 14-year-old girl revealed multiple clonal structural rearrangements with evidence of clonal evolution. The karyotype was 46,XX,del(3)(q27),add(10)(q22),add(12)(p13)/46,idem,t(3;8)(p21;q13 ),add(10) (q26),der(15)del(15)del(15)(q15q22)ins(15;?) q15;?)/46,id em,-X,+2,t(3;8),add(10),der(15). The finding of clonal structural aberrations suggests that fibrous dysplasia is a neoplastic lesion which develops as the result of somatic mutations.

Adolescent↗
PubMed1994

Karyotypic changes in phyllodes tumors of the breast.

Cytogenetic analysis of short-term cultures of five phyllodes tumors of the breast-classified as benign (one tumor), borderline malignant (two tumors removed from the same breast in 1991 and 1993), and malignant (two tumors)--revealed clonal changes with simple structural abnormalities in the benign tumor, the borderline malignant tumors, and one malignant tumor in which benign areas and areas of borderline malignancy were also present. In contrast, the malignant tumor without admixed borderline malignant or benign areas had a complex karyotype. The karyotype of the benign phyllodes tumor was 46,XX,del(12)(p11p12)/46,XX,t(8;18)(p11;p11)/46,XX. The first borderline malignant phyllodes tumor had t(3;20)(p21;q13) as the sole abnormality. When the tumor recurred, this was no longer the only clone detected and the tumor karyotype was now 46,XX,t(3;20)(p21;q13)/46,XX,t(9;10)(p22;q22)/46,XX,t(1;8) (p34;q24)/46,XX,del(11)(q22-23)/46,XX. The malignant/borderline malignant/benign tumor had t(1;6)(p34;p22) as the sole clonal abnormality. Finally, the karyotype of the malignant phyllodes tumor which contained no benign or borderline malignant areas was 42,XX,der(1)t(1;4)(q21;q21),der(3)t(3;17)(q29;q21), -4,i(8)(q10), -10, -13,i(13)(q10),der(14)t(1;14)(q21;p11),der(14)t(4;14) (p12;p11), -17/80-90,idemx2, +del(1)(q12), +i(1)(p10), +dic(5;5)(p14;p14), +i(6)(p10), +del(7)(p11), +dup(7)(q11q36), +i(15)(q10),inc/46,XX. The findings indicate some cytogenetic similarities between benign/borderline malignant phyllodes tumors and fibroadenomas of the breast, presumably reflecting similar pathogenetic mechanisms in the two types of mixed-lineage tumors.

Aged↗
PubMed1994

Chromosome abnormalities in adenolipomas of the breast: karyotypic evidence that the mesenchymal component constitutes the neoplastic parenchyma.

Cytogenetic analysis of adenolipomas of the breast, a tumor type that has not been chromosomally characterized before, revealed the karyotypes 47,XX, +del(1)(p22) in one tumor and 46,XX, t(12;16)(q15;q24) in the other. Breast adenolipomas thus seem to be karyotypically identical to sporadic lipomas in other locations: rearrangements of 12q13-15 are the most common cytogenetic aberrations in lipomas, and also breaks in and around 1p22 have been reported in such tumors. The similarity with lipoma could be documented further in case 2, in which epithelial and mesenchymal cells were cultured separately; the t(12;16) was present in the latter but not in the former. This is evidence that the connective tissue is the neoplastic parenchyma in adenolipomas of the breast, whereas the glandular elements show concomitant but nonneoplastic proliferation.

Adenoma↗