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Biomedical subjects

S Heim

Publications and source records attributed to S Heim.

At least 91 records · Page 5Linked to original sources
PubMed1997

Prognostic impact of bone marrow karyotype in childhood acute lymphoblastic leukaemia: Swedish experiences 1986-91.

The prognostic value of cytogenetic classification in acute lymphoblastic leukaemia (ALL) was evaluated in Swedish children below 16 years of age (n = 372) diagnosed between 1986 and 1991. A bone marrow karyotype was obtained in 281 cases, of which 149 (53%) showed clonal abnormalities. Event-free survival (p-EFS) was 0.64-0.69 in patients with diploid and pseudodiploid karyotype. Patients with massive hyperdiploidy (> 50 chromosomes) had the best outcome (p-EFS = 0.76) and those with hypodiploidy (< 46 chromosomes) had the worst (p-EFS = 0.33). White blood cell count and age were the strongest predictors of outcome. The karyotype reached borderline significance. The diagnostic karyotype was also a predictor of outcome after relapse, with hyperdiploid patients doing better than the others. The presence of a structural chromosomal abnormality did not constitute a negative prognostic factor when intensive chemotherapy was given.

Adolescent↗
PubMed1997

Deletion of the short arm of chromosome 3 in breast tumors.

Deletions in the short arm of chromosome 3 have long been known to be common in many tumor types, including carcinomas of the lung and kidney. Small interstitial deletions of the proximal-central region of 3p, with band 3p14 as a minimal common deleted segment, have recently been shown to occur in as many as 10% of carcinomas of the breast, often as the only chromosomal change. Seemingly identical deletions may also be found in the epithelial cells of mixed-lineage benign tumors of the breast and even in diffuse proliferative breast disease, a disorder that would not normally be accepted as neoplastic, but never in completely normal breast tissue. The cytogenetic evidence therefore indicates that the putative tumor suppressor gene deleted from 3p14 influences cellular proliferation; evidently, its loss is often not sufficient for a fully malignant phenotype to emerge. The first information about FHIT, a candidate suppressor gene recently identified in the FRA3B fragile site in 3p14 and found to be abnormal or lost in a high percentage of carcinomas of various organs, including breast, is compatible with such a general proliferation-regulating role.

Breast Neoplasms↗
PubMed1996

Gain of 17q24-qter detected by comparative genomic hybridization in malignant tumors from patients with von Recklinghausen's neurofibromatosis.

The genetic changes leading to the development of malignant peripheral nerve sheath tumors (MPNSTs) are largely unknown. The few tumors that have been investigated cytogenetically had highly complex karyotypes and no consistent rearrangements, and the attempts to pinpoint consistent DNA-level changes have met with only limited success. We used comparative genomic hybridization to analyze seven MPNSTs and one dermatofibrosarcoma protuberans from eight patients with von Recklinghausen's disease (neurofibromatosis type 1), as well as three sporadic MPNSTs. Gains and losses of DNA sequences were found in all tumors, with an average of four losses (range, 0-14) and two gains (range, 0-5) per tumor. Two striking observations were made: (a) an increase in copy number of the distal part of the long arm of chromosome 17, with the smallest region of overlap 17q24-qter, was seen in five of seven MPNSTs and in the only dermatofibrosarcoma protuberans, all of which were from patients with neurofibromatosis, whereas none of the three sporadic MPNSTs had this alteration; and (b) loss of 13q, with the smallest region of overlap 13q14-q21, was found in 6 of 10 MPNSTs. The consistent involvement of these two chromosomal regions probably reflects two different pathogenetic mechanisms for MPNSTs.

Chromosome Deletion↗
PubMed1996

Correlation between karyotypic pattern and clincopathologic features in 125 breast cancer cases.

A correlation analysis was performed on 125 cytogenetically characterized breast cancer cases to assess the relationship between the tumor karyotype and clinicopathologic features. The carcinomas of young women had a higher modal chromosome number than those of older women. The number of chromosomal aberrations and modal chromosome number were also found to correlate with the histologic type, grade and mitotic activity of the tumor. Whereas all lobular carcinomas were karyotypically normal or near-diploid, more than 3 aberrations and sometimes near-triploid or near-tetraploid karyotypes were common findings in ductal carcinomas, especially in grade-III tumors and in tumors showing high mitotic activity in vivo. Karyotypes with cytogenetically unregulated clones and unbalanced structural chromosomal rearrangements were more frequent in infiltrating than in in situ carcinomas but, at least as far as the second of these 2 characteristics is concerned, especially in infiltrating carcinomas that also had an in situ component. The presence of cytogenetic polyclonality correlated with tumor grade. Although recurrent chromosome aberrations were significantly more common in ductal than in lobular carcinomas, none of these breast cancer-associated anomalies seemed to be specific for any particular clinicopathologic parameter. The associations between modal chromosome number and mitotic activity and between cytogenetic polyclonality and tumor grade were found to be statistically significant in multivariate models. No correlations was seen between the karyotypic findings and tumor size or the presence of axillary-lymph-node metastases.

Adult↗
PubMed1996

Karyotypic comparisons of multiple tumorous and macroscopically normal surrounding tissue samples from patients with breast cancer.

Many tumor tissues are made up of genetically different cell populations, and the study of the causes and consequences of this heterogeneity must play a central role in cancer research. We have studied breast cancer clonal heterogeneity by cytogenetic analysis of 4123 cells from 52 successfully short-term-cultured tumorous, metastatic, and macroscopically normal breast tissue samples from 6 women with this disease. All 7 carcinomas (one woman had bilateral disease) contained 1 to 9 karyotypically related as well as unrelated clones, unevenly distributed among the tumor quadrants. Two clonal chromosome abnormalities were recurrent: interstitial 3p deletions were found in 5 carcinomas, whereas del(1)(q42) was detected in another 2 tumors. Both successfully analyzed metastatic lesions (one axillary lymph node and one metastasis in the subcutis) contained only one of several clones present in the primary tumor, thus exemplifying a reduction in overall karyotypic complexity during carcinoma spreading. In the case with the cytogenetically abnormal lymph node, another karyotypically unrelated clone was found to invade locally in the surrounding breast; also, histological evidence of carcinoma infiltration was seen in these tissue samples. In none of the other cases were clonal karyotypic changes found in macroscopically normal, extratumorous breast tissue. We conclude that a large proportion of breast carcinomas are polyclonal with cytogenetically distinct cell subpopulations expanding within separate domains of the growing tumor. Karyotypically disparate neoplastic cells may have different capacities to display malignancy-specific features (e.g., to grow invasively and set up distant metastases). It is presumed that their synergetic action is required for the full-blown carcinoma phenotype.

Adult↗
PubMed1996

Clonal chromosome abnormalities in two chemodectomas.

Short-term cultures from two histologically benign chemodectomas, one from the carotid body and one from the vagal nerve, were analyzed cytogenetically. The former had a small abnormal clone with the karyotype 46,XX,t(3;19)(q21;q13),t(12;15) (p13;q12-14), whereas the majority of the cells from the latter tumor displayed two related abnormal clones: 46,XY,i(I)(q10)/ 46,iderm,add(2)(q37). The findings add to the evidence that chemodectomas are heterogeneous neoplasms and suggest that the heterogeneity may possibly be associated with the site of origin.

Carotid Body Tumor↗
PubMed1996

Different cytogenetic patterns in skeletal breast cancer metastases.

Short-term cultures of breast cancer metastases to bone from two patients were analyzed cytogenetically. One metastasis had a complex hypotriploid karyotype with numerous marker chromosomes, whereas the other had simple karyotypic changes in three unrelated clones, 46,XX,t(4;11 )(p14;p 13)/45,XX,- 19/46,XX,del(3)(p 13p23), suggesting that the metastasis had originated from a simultaneous invasion of multiple cells from the primary tumor. The metastasis with complex chromosomal aberrations developed quickly as part of a clinically aggressive disease, whereas that with simple changes developed more than 20 years after the initial breast cancer diagnosis. Our findings therefore indicate that the tumor karyotype may play a role in determining the clinical course in patients with breast cancer.

Bone Neoplasms↗
PubMed1996

Cytogenetic abnormalities in an in situ ductal carcinoma and five prophylactically removed breasts from members of a family with hereditary breast cancer.

Short-term cultures of tissue samples from three bilateral prophylactic mastectomies and one in situ ductal carcinoma from four women belonging to a family with hereditary breast cancer were cytogenetically analyzed. Clonal chromosome abnormalities were detected in five of the six prophylactically removed breasts, all of which had the histologic diagnosis epithelial hyperplasia without atypia, and in the in situ carcinoma. The same karyotypic imbalance, a loss of 3p12-14, was detected in the in situ carcinoma as well as in one of the hyperplasias, indicating that these bands may harbor a pathogenetically relevant gene in this breast cancer family. The finding of chromosome aberrations in clonal proportions in the prophylactically removed breasts indicates that a neoplastic process was already present, lending support to the view that prophylactic bilateral mastectomy in these high-risk individuals prevented the development of breast carcinoma.

Breast Neoplasms↗
PubMed1996

Cytogenetic findings in four malignant mixed mesodermal tumors of the ovary.

Short-term cultures of four malignant mixed mesodermal tumors of the ovary were cytogenetically analyzed. The primary tumor was examined in three cases, whereas in one case the sample was obtained from a residual tumor mass after chemotherapy. The tumor sampled after cytostatic treatment had a relatively simple karyotype with numerical changes that included pentasomy 12 and an i(1)(q10) as the only structural abnormality. Karyotypic analysis of the three primary tumors revealed extensive structural as well as numerical aberrations, i.e., a picture similar to that seen in the few malignant mixed mesodermal tumors with karyotypic anomalies described previously. Rearrangements of chromosome 1, leading to loss of distal 1p, and homogeneously staining regions have so far been the most frequent cytogenetic changes in this tumor type. Malignant mixed mesodermal tumors of the ovary thus seem to be karyotypically identical to the more numerous mixed mesodermal tumors of uterine origin, and they do not differ substantially in this respect from pure ovarian carcinomas.

Chromosome Aberrations↗
PubMed1996

No FISH evidence for trisomy 7 in normal or leukemic bone marrow.

Trisomy 7 has been found as the sole chromosomal anomaly in both benign and malignant tumors, as well as in nonneoplastic lesions. It has been reported that +7 may occur in tumor-infiltrating as well as in peripheral T cell and in the thymus. The precursor cells, which mature in the thymus to T lymphocytes, originate in the bone marrow and the present study was undertaken to investigate whether cells carrying an extra chromosome 7 can be detected there. Bone marrow samples from five hematologically normal individuals and 12 children with acute lymphoblastic leukemia (ALL) were analyzed by interphase fluorescence in situ hybridization (FISH) using a chromosome 7 centromere-specific probe. Half of the ALLs were karyotypically normal, whereas the other half displayed clonal abnormalities (one pseudodiploid and five hyperdiploid karyotypes, none of which had +7). The FISH analysis showed no evidence of cells with trisomy 7 in the bone marrow samples from the controls or ALLs. This suggests that the gain of a chromosome 7 by T lymphocytes does not occur before the bone marrow precursor cells are conditioned in the thymus.

Adolescent↗
PubMed1996

Chromosome abnormalities in colorectal adenomas: two cytogenetic subgroups characterized by deletion of 1p and numerical aberrations.

Cytogenetic analysis of short-term cultures from 34 benign colorectal polyps, all histologically verified as adenomas, revealed clonal chromosome aberrations in 21 of them. Eight polyps had structural rearrangements, whereas only numerical changes were found in 13. A combination of structural and numerical chromosomal aberrations was found in three polyps. The most common numerical change was gain of chromosome 7, found either as the sole anomaly (five polyps), together with other numerical changes (six polyps), or together with structural rearrangements (two polyps). Other recurrent numerical changes were +20, +13, and monosomy 18, found in six, five, and two adenomas, respectively. Rearrangement of chromosome 1 was the most common structural change. Abnormalities involving 1p were seen in six adenomas, leading to visible loss of material in three. One adenoma had one clone with a large and another with a small 1p deletion. In three adenomas, del(1)(p36) was the only cytogenetic aberration, supporting the authors' previous conclusion that loss of one or more gene loci in band 1p36 is a common early change in colorectal tumorigenesis. Chromosome 8 was involved in structural changes in two adenomas; in one this led to loss of 8p and in the other to gain of 8q. The cytogenetic findings did not correlate in a statistically significant manner with clinicopathologic parameters, such as grade of dysplasia, macroscopic or microscopic adenoma structure, tumor size and location, or the patients' sex and age.

Adenoma↗
PubMed1996

Karyotypic characteristics of borderline malignant tumors of the ovary: trisomy 12, trisomy 7, and r(1) as nonrandom features.

Clonal karyotypic abnormalities were detected in five of 14 cytogenetically analyzed borderline malignant ovarian tumors of clinical stages I-II. One mucinous and one seropapillary tumor had trisomy 7 and r(1)(p36q42) as the sole chromosome abnormality, respectively. Trisomy 12 was found in the remaining three cases. It was the only change in one mucinous and one serous tumor, whereas the third, a seropapillary borderline tumor, had the karyotype 49,XX,+5,+8, +12. These findings, especially when collated with those of previous reports on ovarian borderline tumor cytogenetics, indicate that +12 is the most consistent chromosomal aberration in this group of neoplasms and that also +7 and r(1) are nonrandom features. From the karyotypic point of view, benign ovarian tumors and well-differentiated carcinomas are similar to borderline ovarian tumors, with the possible exception that the former have no tendency to form r(1). Highly malignant carcinomas, on the other hand, are typically much more complex. Chromosome-level changes therefore cannot account for the putative phenotypic passage through the most innocuous tumor stages as epithelial ovarian neoplasms go from benign to fully malignant.

Adenocarcinoma, Mucinous↗
PubMed1996

t(3;21)(q26;q22) with AML1 rearrangement in a de novo childhood acute monoblastic leukaemia.

t(3;21)(q26;q22) is a recurrent chromosomal abnormality in Philadelphia-positive chronic myeloid leukaemia in blast crisis and in treatment-related myelodysplastic syndrome and acute myeloid leukaemia. The molecular consequences of the t(3;21) are presently being unravelled; various transcripts between the AML1 gene in 21q22 and several unrelated genes, i.e. EAP, EVI1 and MDS1, in 3q26 are generated, resulting in the formation of a chimaeric transcription factor. The t(3;21) has only rarely been described in de novo leukaemias and never before in an acute leukaemia in a child. We here present the clinical, cytogenetic and molecular genetic findings in a boy with a de novo acute monoblastic leukaemia with t(3;21)(q26;q22) and AML1 rearrangement.

Blotting, Southern↗
PubMed1996

Clonal chromosome abnormalities in neoplastic cells: evidence of genetic instability?

All types of neoplasia that have been extensively examined, be they benign or malignant, are characterized by acquired chromosomal aberrations. In many instances, the changes are specific for the tumour type in question. Some tumours, even among the most malignant ones, have only a single chromosomal abnormality, whereas others have numerous secondary aberrations. Although an overall parallel exists between a tumour's malignancy and the number and complexity of its chromosomal changes, in some situations altered selection pressure may give rise to reduced karyotypic complexity with time. The effective causes of both primary and secondary chromosomal changes of neoplastic cells are largely unknown. In some special situations, in particular therapy induced acute leukaemias, exposure to a carcinogenic agent seems to have specifically induced the leukaemogenic genetic rearrangement. Patients carrying malignant neoplasms have in most studies been found to have normal chromosomal stability in their non-neoplastic somatic cells, both generally and at the genomic regions that are rearranged in their tumours. Although abnormal chromosomal fragility of cells belonging to the neoplastic parenchyma has not been convincingly demonstrated, the existence of such instability remains a viable, perhaps even necessary, hypothesis. To look for a unifying mechanism common to all neoplastic processes seems simplistic: specific mutagenesis giving rise to both primary and secondary chromosomal changes is likely to occur in some tumours, whereas in others random aberrations are generated, and at least as far as the secondary ones are concerned often at a higher than normal rate, followed by Darwinian selection for fitness within the host organism.

Acute Disease↗