[The Preventive Home Visit as a Preventive Intervention to Reach the Elderly--Effectiveness and Cost-Effectiveness of Different Ways of Approach]. / Der präventive Hausbesuch als zugehende Präventionsmaßnahme im Alter--Effektivität und Kosteneffektivität von Zugangswegen.

The aim of the study was a systematical further development of targeted approaches. Research questions were how elderly women and men could be motivated to participate in a preventive intervention and by which approaches elderly with different health risks could be reached. In several stages a specific motivational material was developed. Afterwards two different approaches to the elderly (general practice, health insurance) were tested and evaluated considering its (cost) effectiveness.

Differential role of the Mentalizing and the Mirror Neuron system in the imitation of communicative gestures.

Successful social interaction requires recognising the intention of another person's communicative gestures. At a neural level, this process may involve neural activity in different systems, such as the mentalizing system (MS) and the mirror neuron system (MNS). The aim of the present study was to explore the neural correlates of communicative gestures during observation and execution of these gestures. Twenty participants watched video clips of an actor executing social gestures (S), non-social gestures (NS) and meaningless gestures (ML). During fMRI data acquisition, participants were asked to observe (O) and subsequently to execute (E) one of two tasks: imitate the gesture presented (IMI) or perform a motor control task (CT). For the contrast IMI>CT we found activations in the core areas of the MNS [inferior parietal lobule (IPL) and inferior frontal cortex, the posterior part of pars opercularis], as well as in areas related to the MS [superior temporal sulcus (STS) and middle cingulate cortex]. For S>NS, we found activations in the left medial orbitofrontal cortex (mOFC), right superior frontal cortex and middle cingulate cortex. The interaction of stimulus condition (S vs NS) and task (IMI vs CT) revealed activation in the right IPL. For the interaction between observation vs execution (O vs E), task (IMI vs CT) and stimulus condition (S vs NS) we found activation in the right mOFC. Our data suggest that imitation is differentially processed in the MNS as well as in the MS. The activation in IPL is enhanced during the processing of social gestures most likely due to their communicative intention. The activation of IPL together with medial frontal areas may contribute to mentalizing processes. The interaction in the mOFC suggests an involvement of self-referential processes in the processing of social gesture.

Molecular cytogenetic analysis of a gliosarcoma with osseous metaplasia.

Gliosarcoma, a rare glioblastoma variant, is composed of a glial and a mesenchymal component. Though the mesenchymal portion most commonly resembles a fibrosarcoma, other differentiation patterns have been observed. We present the first genomic characterisation (karyotyping followed by FISH and array comparative genomic hybridisation analysis) of a gliosarcoma with osseous metaplasia. In addition to chromosomal changes often found in gliomas (+7, -10, -13, and -22), the tumour cells also harboured a hitherto unknown t(3;21)(q13∼21;q21∼22).

Dual function of the selenoprotein PHGPx during sperm maturation.

The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) changes its physical characteristics and biological functions during sperm maturation. PHGPx exists as a soluble peroxidase in spermatids but persists in mature spermatozoa as an enzymatically inactive, oxidatively cross-linked, insoluble protein. In the midpiece of mature spermatozoa, PHGPx protein represents at least 50 percent of the capsule material that embeds the helix of mitochondria. The role of PHGPx as a structural protein may explain the mechanical instability of the mitochondrial midpiece that is observed in selenium deficiency.

Tiling resolution array CGH of dic(7;9)(p11 approximately 13;p11 approximately 13) in B-cell precursor acute lymphoblastic leukemia reveals clustered breakpoints at 7p11.2 approximately 12.1 and 9p13.1.

The dic(7;9)(p11 approximately 13;p11 approximately 13) is a recurrent chromosomal abnormality in acute lymphoblastic leukemia (ALL), mainly of B-lineage. Although more than 20 dic(7;9)-positive ALLs have been reported to date, the molecular genetic consequences of this aberration are unknown. We performed tiling resolution (32K) genome-wide array-based comparative genomic hybridization (array CGH) analysis of three cases with dic(7;9) in order to characterize the breakpoints on 7p and 9p. The analysis showed a clustering of breakpoints within 9p13.1 in all three cases and within 7p11.2 in two cases; the array CGH revealed two different breakpoints - 7p12.1 and 7p14.1 - in the remaining case. Based on these findings the abnormality should hence be designated dic(7;9)(p11.2 approximately 12.1;p13.1). Locus-specific fluorescence in situhybridization analysis of one of the cases narrowed down the 7p11.2 breakpoint to a <500-kb segment in this sub-band, a region containing three known genes. Unfortunately, lack of material precluded further molecular genetic studies, and it thus remains unknown whether the pathogenetically important outcome of the dic(7;9) is formation of a chimeric gene or loss of 7p and/or 9p material.

FISH mapping of i(7q) in acute leukemias and myxoid liposarcoma reveals clustered breakpoints in 7p11.2: implications for formation and pathogenetic outcome of the idic(7)(p11.2).

Isochromosome 7q - i(7q) - is seen in a wide variety of hematologic malignancies and solid tumors, often as a secondary change to a characteristic primary translocation. Despite its high frequency, nothing is known about the formation and the pathogenetic outcome of this abnormality. To address these issues, we performed a detailed fluorescence in situ hybridization (FISH) investigation of four acute lymphoblastic leukemias, one acute myeloid leukemia, and two myxoid liposarcomas with i(7q). Using FISH with bacterial artificial chromosomes (BACs) mapping between 7p12.2 and 7q11.2, the breakpoints (BPs) in all seven cases were shown to cluster to an approximately 340 kb segment at 7p11.2, covered by the overlapping BAC probes RP11-760D2 and RP11-10F11. Thus, the i(7q) should formally be designated idic(7) (p11.2). In one of the cases, FISH with fosmids could narrow down the BP further to an 80-kb sequence delineated by G248P81983A10 and G248P8793H7. No known genes are located in the 340-kb BP cluster region, indicating that the idic(7)(p11.2) does not result in a fusion or deregulation of genes in this segment. The pathogenetically important outcome is thus likely to be an altered gene expression because of copy number changes. The clustering of breakpoints might be due to frequent intrachromosomal duplicons in the BP region.

Consistent involvement of only 71 of the 329 chromosomal bands of the human genome in primary neoplasia-associated rearrangements.

In an attempt to quantify the nonrandomness of primary neoplasia-associated acquired chromosomal aberrations in humans, we have retrieved information from a computerized data base on the chromosomal abnormalities of 9069 human neoplasms. By restricting the survey to the 1985 cases with a solitary structural rearrangement, we attempted to limit the analysis to only those aberrations that were most likely to represent pathogenetically important, primary changes. The breakpoints of the primary abnormalities thus identified clustered to 71 bands. It furthermore turned out that 27 of the 41 oncogene sites known with reasonable precision (i.e., localized within one or two bands) coincide with bands consistently involved in neoplasia-associated rearrangements. These comparisons add to the evidence that acquired, cancer-associated chromosomal aberrations are nonrandom in distribution, that only a limited number of genomic sites are consistently involved in primary neoplasia-associated aberrations, and that the concordance between the breakpoints of primary aberrations and the location of cellular oncogenes is greater than predicted by chance.

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.

Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis.

Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural rearrangements were found that led to loss of genetic material from 1p. In three of the cases, the deletion was restricted to the 1p36 band; the rest had lost larger 1p segments. The rearrangement of chromosome 1 was the sole karyotypic anomaly in three adenomas, all with mild or moderate dysplasia, and in the hyperplastic polyp. Both adenomas that had additional aberrations beyond the 1p loss showed severe dysplasia. We conclude that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis. The fact that the adenomas with 1p- as the sole change showed only mild or moderate dysplasia and that the del(1p) was found also in the hyperplastic polyp suggests that this aberration is more related to the induction of hyperproliferation than to differentiation disturbances in the intestinal mucosa.

Chromosome abnormalities in eighty-three head and neck squamous cell carcinomas: influence of culture conditions on karyotypic pattern.

Short-term cultures from 115 squamous cell carcinomas (SCC) of the head and neck were cytogenetically investigated. Thirty-six of the tumors have been reported previously, whereas 79 are new cases. The material was divided into two series based on the medium used. The 80 tumors of series I were cultured in RPMI 1640 supplemented with fetal calf serum, glutamine, antibiotics, insulin, cholera toxin, and epidermal growth factor. The 35 tumors of series II were cultured in a chemically defined, serum-free medium with a low calcium concentration, MCDB 153, which stimulates epithelial growth while inhibiting fibroblasts. A total of 83 tumors with clonal karyotypic abnormalities were detected in the two series. Series II had a higher proportion of tumors with complex karyotypic changes than series I (43% versus 15%), a lower proportion of tumors with pseudo- or neardiploid clones characterized by simple rearrangements (3% versus 34%), and a lower frequency of unrelated clones (3% versus 24%), indicating that the different culture conditions favored growth of different cell populations. Except for rearrangements of 1p22, which were mainly found in series I, the distribution of breakpoints in structural aberrations was similar in the two series and clustered to several chromosomal bands or regions, in particular 11q13, 1p22, 1p11-12, 3p11-q11, 5q13, 1q25, 15q10, and 8q10. Unbalanced structural aberrations were more common in series II, frequently leading to loss of segments from chromosome arms 3p, 7q, 8p, 11q, 13p, 14p, and 15p, whereas gain of genetic material often involved chromosome arms 1q, 3q, 8q, and 15q.

Identification of cytogenetic subgroups and karyotypic pathways in transitional cell carcinoma.

The clinical course in urinary bladder cancer is difficult or impossible to predict based on conventional disease parameters. It is a reasonable hypothesis that the genetic aberrations acquired by the tumor cells, being instrumental in bringing about the disease in the first place, may also hold the key to more reliable prognostication. However, though 200 transitional cell carcinomas (TCC), the most common bladder cancer in the Western world, with clonal chromosomal abnormalities have been reported, our knowledge about the karyotypic characteristics of these tumors remains insufficient. The aberration pattern is clearly nonrandom, but no completely specific primary or secondary karyotypic abnormality has been identified, and the chronological order in which the aberrations appear during disease progression is not well known. The high degree of karyotypic complexity in epithelial tumors like TCC is one reason why our picture of the sequential order of cytogenetic evolution is unclear. To overcome some of these difficulties we have used several statistical methods that allow analysis and interpretation of the relationship between cytogenetic aberrations in TCC. We show that there exists a temporal order with respect to the appearance of chromosomal imbalances and that this order is highly correlated with tumor stage and grade. Analyzing changes in the distribution of imbalances per tumor in G1, G2, and G3 tumors, we suggest that progression involves the acquisition of cytogenetically detectable and submicroscopic genetic changes at comparable frequencies. By means of computer simulations, we show that the imbalances -9, +7, and 1q+ appear earlier than expected from random events and that -6q, -5q, -18, +5p, -22p, and -15 appear later than expected. Using principal component analysis, we identify two cytogenetic pathways in TCC, one initiated by -9 and followed by -11p and 1q+, the other initiated by +7 and followed by 8p- and +8q. The -9 pathway was correlated with stage Ta-T2 tumors, whereas the +7 pathway was correlated with stage T1-T3 tumors, i.e., +7 tumors appeared to be more aggressive. Although these pathways are well separated at earlier stages, they later converge to contain a common set of imbalances.

Cytogenetic analysis of 33 basal cell carcinomas.

Cytogenetic analysis of short-term cultures from 33 basal cell carcinomas (BCC), a type of neoplasm for which no previous karyological data exist, revealed clonal chromosome aberrations, all of them different, in 8 tumors. In 2 cases, 2 cytogenetically unrelated clones were detected, suggesting a multicellular origin in at least a subset of BCC. A remarkably high level of nonclonal structural rearrangements, mostly in the form of seemingly balanced translocations, was found in 23 tumors; namely, in 6 of 8 BCC with clonal karyotypic abnormalities and in 17 of 25 without. It is possible that some of these aberrations represent additional neoplastic clones, thus indicating an even higher level of cytogenetic heterogeneity in BCC. We think that the most likely interpretation of the results is that BCC may have a multicellular origin, reflecting field cancerization of the skin. During subsequent tumor development, the selection pressure narrows down the number of clones that infiltrate the surrounding tissue. The finding by karyotypic analysis of some apparently monoclonal, some polyclonal BCC, may reflect that different tumors have been examined at different points in the clonal evolution of the neoplastic cells.

Nonrandom chromosome abnormalities in short-term cultured primary squamous cell carcinomas of the head and neck.

We report the finding of clonal chromosome abnormalities in short-term cultures from 44 squamous cell carcinomas of the head and neck region. Eleven tumors had gain or loss of the Y chromosome, sometimes one clone with +Y and another with -Y, as the sole anomaly, whereas the remaining 33 all carried structural rearrangements and usually were cytogenetically complex with multiple aberrations. The chromosomal bands most frequently involved were, in decreasing order of frequency, 8p11-q11, 1p11-q11, 3p11-q11, 11q13, 13p11-q11, 1p13, 5p11-q11, 7p11-q11, 15p11-q11, and 14p11-q11. Almost one-half of the breakpoints were located in centromeric or juxtacentromeric bands. Recurrent aberrations included i(8q), i(5p), i(1q), del(3)(p11-12), del(5)(p11), t(1;1)(p13;q25), and der(14;15)(q10;q10). To see whether the karyotypic features of head and neck squamous cell carcinoma differ depending on exact tumor site, we added to the present series our previously published 23 karyotypically abnormal head and neck squamous cell carcinomas that had been cultured in the same way as the tumors of the present series. In the ensuing correlation analysis, tumors of the oral cavity and oropharynx and hypopharynx were found to share many features: highly complex karyotypes were frequent, often containing isochromosomes such as i(8q) and i(5p), and also rearrangements of 11q13 (often as homogeneously staining regions) and loss of genetic material from the short arms of chromosomes 3, 13, 14, and 15 were repeatedly seen. Laryngeal carcinomas, on the other hand, often had simple karyotypic changes.

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.

The reciprocal translocation t(9;16)(q22;p13) is a primary chromosome abnormality in basal cell carcinomas.

The reciprocal translocation t(9;16)(q22;p13) was identified in three short-term cultured basal cell carcinomas (BCCs). The t(9;16) was the sole anomaly in one clone in two tumors and was accompanied by a second change that also affected the long arm of chromosome 9 in the third. In addition, other cytogenetically unrelated abnormal clones were also found in all three BCCs. The identification of t(9;16)(q22;p13) as a primary chromosomal abnormality in a subset of BCCs (we found it in 3 of 22 tumors) is especially intriguing against the background that the PTCH gene, which when mutated in the germ line presumably gives rise to the autosomal dominant basal cell nevus or Gorlin's syndrome, maps to chromosome band 9q22. None of the genes rearranged in the BCC-specific t(9;16)(q22;p13) translocation have been identified, but we hypothesize that the translocation represents the cytogenetic corollary of a tumorigenic recombination of PTCH with an as yet unknown gene in 16p13. If so, this would be the first time that a tumor suppressor gene causally involved in a hereditary cancer is shown to be frequently rearranged through a specific translocation in sporadic carcinomas of the same type.

DNA copy number changes in malignant ovarian germ cell tumors.

Malignant ovarian germ cell tumors (OGCTs) include immature teratomas (ITs), dysgerminomas (DGs), endodermal sinus tumors (ESTs), choriocarcinomas, and embryonal carcinomas. Knowledge about the genetic changes associated with malignant OGCT development is sparse. We therefore analyzed 25 OGCTs (12 DGs, 4 ESTs, and 9 ITs) for gains and losses by comparative genomic hybridization. In total, more gains than losses were observed, and the number of alterations ranged from 0-20 per tumor. The average number of changes among DGs, ESTs, and ITs was 10, 6, and 1.4, respectively. The most common changes in DGs were gains from chromosome arms 1p (33%), 6p (33%), 12p (67%), 12q (75%), 15q (42%), 20q (50%), 21q (67%), and 22q (58%); gains of the whole of chromosomes 7 (42%), 8 (42%), 17 (42%), and 19 (50%); and losses from 13q (58%). Two of three DGs with a gonadoblastoma component showed gains of 3p21 and loss of 5p, whereas none of the nine pure DGs had these changes, suggesting that they might be characteristic either of gonadoblastoma or of DG developing from a gonadoblastoma. Gain of 12p and gain from 1q were seen in three of four ESTs, whereas gains from 3p, 11q, and Xp and loss from 18q were each found in two tumors. Five of the ITs revealed changes (range, 1-4 changes/tumor), with gains from 1p, 16p, 19, and 22q each being found in two tumors. We conclude that ovarian DGs and ESTs seem to develop via the same genetic pathways that are already known for testicular germ cell tumors. On the other hand, ITs do not exhibit gain of 12p and also typically show fewer changes than other malignant OGCTs, indicating that they arise via different pathogenetic mechanisms.

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.

Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11).

Although most extraskeletal myxoid chondrosarcomas (EMC) are cytogenetically characterized by the translocation t(9;22)(q22;q12), another subset has recently been identified carrying a t(9;17)(q22;q11). Whereas the t(9;22) is known to result in fusion of the CHN (TEC) gene from 9q22 with the EWS gene from 22q12, creating a chimeric EWS/CHN, the genes involved in the t(9;17) of EMC are unknown. We examined two EMC with t(9;17)(q22;q11) and found that the CHN gene was recombined with the RBP56 gene from 17q11 to generate a chimeric RBP56/CHN. RBP56 has not previously been shown to be involved in tumorigenesis but it encodes a putative RNA-binding protein similar to the EWS and FUS (TLS) proteins known to play a pathogenetic role in several sarcomas. The presence of the RBP56/CHN chimeric gene in EMC with t(9;17)(q22;q11) shows that the N-terminal parts of EWS and RBP56 have similar oncogenic potential making them pathogenetically equivalent in oncoproteins arising from fusions with certain transcription factors.

Primary chromosome abnormalities in human neoplasia.

At the cellular level, cancer is a genetic disease; genetic changes in somatic cells are essential events in neoplasia. In a majority of cases these changes involve large enough blocks of genetic material to be visible in the microscope. The chromosome aberrations in neoplastic disorders are probably of three kinds: (1) primary abnormalities, which are essential steps in establishing the tumor; (2) secondary abnormalities, which develop only after the tumor has developed, but which nevertheless may be important in tumor progression; and (3) cytogenetic noise, which is the background level of nonconsequential aberrations. These latter changes are, in contrast to the primary and secondary changes, randomly distributed throughout the genome. The primary abnormalities, of which several dozens have now been identified, are mostly strictly correlated with particular diseases and even with histopathological subtypes within a given disease. This has been evident in the leukemias for some years already, and information now accumulating on solid tumor karyology indicates a similar situation. Clonal chromosome abnormalities are a feature of both benign and malignant neoplasms, although the changes are often less massive in the former. Apart from being clinically useful as a diagnostic technique and an aid in prognostication, tumor cytogenetics also plays a role in identifying those genomic sites which harbor genes essential in the pathogenesis of neoplastic lesions. So far, two functionally different classes of directly cancer-relevant genes have been detected, the oncogenes and antioncogenes. There is every reason to believe that future investigations with cytogenetic and recombinant DNA methods will add to our knowledge of the biology of human neoplasia, in those tumor types where the characteristic genetic change is already partially known, and by identifying hitherto unknown karyotypic abnormalities.

Cytogenetically unrelated clones in hematological neoplasms.

We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression.