Biomedical subjects

K Broberg

Publications and source records attributed to K Broberg.

7 recordsLinked to original sources

PubMed2001

Analysis of the distribution and frequency of trisomy 7 in vivo in synovia from patients with osteoarthritis and pigmented villonodular synovitis.

Osteoarthritis (OA) and pigmented villonodular synovitis (PVNS) are disorders associated with trisomy 7. The aim of the present study was to determine the frequency and distribution of the cells with +7 in vivo by analyzing sections of paraffin-embedded synovia from patients affected by OA, PVNS, other forms of synovitis [hemorragic synovitis (HS) and chronic synovitis (CS)], and from individuals without joint disease. Fluorescence in situ hybridization (FISH), using a centromeric probe for chromosome 7, showed that the mean frequency of trisomic nuclei in 5-microm sections was highest in PVNS (9.0%), followed by CS (5.9%), OA (5.6%), and HS (4.6%), whereas trisomic nuclei were rare (0.7%) in normal tissue. When 8-microm sections were studied, the frequencies of trisomic cells in OA and control synovia increased to 6.7% and 1.5%, respectively. Trisomic nuclei were found in all cases, including those for which cytogenetic analysis of short-term cultures had not disclosed any trisomic cells. Overall, the trisomic cells were scattered within the tissue. However, small clusters of cells with +7 were found in three cases. By hematoxylin-eosin staining of the slides used for FISH analysis it could be shown that the clustered trisomic cells were proliferating synoviocytes within villous extensions of the synovial membrane.

Adult↗

PubMed2001

The tumor-associated gene HMGIC is expressed in normal and osteoarthritis-affected synovia.

Chromosomal rearrangements involving chromosome bands 12q13-15 are very frequent findings in benign solid tumors, and recently, the primary molecular target for these aberrations was identified as the gene HMGIC. However, mutations in this gene have also been observed in nonneoplastic tissues. In a previous study, we reported breakpoints within HMGIC of synovia affected by osteoarthritis (OA) in two cases with 12q15 aberrations. To analyze further the role of HMGIC in this disease, we have performed cytogenetic, fluorescent in situ hybridization (FISH), RNA, and protein expression analyses on synovial samples from patients with OA and individuals without signs of the disorder. Cytogenetic analysis of short-term cultured cells revealed clonal 12q13-15 aberrations in 2/36 cases of OA synovia and no rearrangement in any of the five controls. With FISH analysis, it was shown that the chromosomal breakpoints in the two aberrant cases were located outside the HMGIC locus. In contrast, at RNA and protein expression analyses, OA-affected as well as normal synovia displayed transcription and translation of the gene. We also analyzed whether immunoreactivity for HMGIC was associated with the proliferation-specific antigen Ki-67, but no correlation between the staining patterns of these proteins was observed. From the results of the present study, it is evident that expression of HMGIC cannot simply be considered a sign of neoplasia or an effect of proliferation.

Adolescent↗

PubMed2001

Trisomy 7 accumulates with age in solid tumors and non-neoplastic synovia.

Trisomy 7 is a common finding in benign and malignant solid tumors, in several non-neoplastic lesions (for example, osteoarthritis and rheumatoid arthritis), and in apparently normal tissues as well, suggesting that the occurrence of +7 might be associated with factors other than the disease process itself. To find out whether the frequency of +7 varies with a patient's age, we cytogenetically analyzed short-term-cultured synovial samples from elderly persons without signs of arthritis and from young patients affected by juvenile chronic arthritis (JCA). In normal synovia, gain of a chromosome 7 was present as a clonal change in five of 10 cases and in single cells in four of the five remaining cases. In synovia from patients with JCA, cells with +7 were detected in only one of nine cases, representing the oldest patient in the series. Furthermore, we reviewed the cytogenetic literature on tumors of the brain, breast, colon, kidney, lung, skin, thyroid, and upper aerodigestive tract. In the majority (six of eight) of these tumor types, the frequency of cases displaying a clone with +7 as the sole aberration increased with age. Taken together, the results presented here suggest that the acquisition of trisomy 7 in some neoplastic and non-neoplastic tissues might be associated with age rather than with disease. The finding of a completely different frequency distribution in two of the tumor types (tumors of the brain and the thyroid gland), however, emphasizes the heterogeneity of +7 and indicates that other, possibly tissue-specific, factors might influence the occurrence of this mutation.

Adolescent↗

PubMed1999

Cytogenetic polyclonality in hematologic malignancies.

The present study was undertaken to ascertain the frequency of cytogenetic polyclonality in various hematologic malignancies and to investigate whether morphologic subgroup, age, gender, or previous genotoxic exposure influences the incidence. Among 2,243 cytogenetically investigated hematologic malignancies, 10 acute myeloid leukemias (AML), 5 myelodysplastic syndromes (MDS), 2 acute lymphoblastic leukemias (ALL), 1 acute undifferentiated leukemia (AUL), 1 atypical Philadelphia chromosome-negative (Ph-) chronic myeloid leukemia (CML), 1 chronic myeloproliferative disorder (CMD), and 1 chronic lymphoproliferative disorder (CLD) with karyotypically unrelated clones were identified, constituting 2.6% of AML, 1.6% of MDS, 0.8% of ALL, 13% of AUL, 9.1% of Ph- CML, 1.5% of CMD, and 2.8% of CLD with chromosomal abnormalities. In contrast to the cytogenetic features, the X-inactivation pattern was monoclonal in the two informative female patients that could be investigated. Among 17,733 karyotypically aberrant published cases surveyed, significant frequency differences (P < 0.001) were discerned: 1.7% of 6,526 AML, 3.4% of 2,391 MDS, 0.4% of 1,920 Ph+ CML, 2.9% of 856 CMD, 0.9% of 4,226 ALL, and 5.8% of 1,814 CLD displayed unrelated clones. The incidence of cytogenetic polyclonality did not differ significantly among the MDS, CMD, or ALL subgroups, between males and females, between children (< 16 years) and adults, or between B- and T-cell ALL, whereas the frequencies varied among the AML FAB types (P < 0.05), among the different CLD entities (P < 0.001), and between B- and T-cell CLD (P < 0.001). Furthermore, the incidence was higher in therapy-related AML and MDS than in de novo AML and MDS (P < 0.001 and P < 0.01, respectively).

Adolescent↗

PubMed1999

Rearrangement of the neoplasia-associated gene HMGIC in synovia from patients with osteoarthritis.

The occurrence of clonal chromosome aberrations in short-term cultures from synovia, osteophytes, and cartilage from patients with osteoarthritis (OA) was recently reported. Among these aberrations, a recurrent involvement of chromosome bands 12q13-15 in structural rearrangements was detected in both synovia and osteophytes. Chromosomal abnormalities of 12q13-15 are frequent among malignant and benign mesenchymal tumors, and it was recently demonstrated that the molecular target in these neoplasms is the HMGIC gene. In this study, we show by fluorescence in situ hybridization that HMGIC was disrupted by rearrangements of 12q15 in synovia from two patients with OA. The finding of HMGIC rearrangement in a lesion that is not traditionally regarded as neoplastic not only widens the spectrum of disorders that may be associated with altered function of this gene, but also provides further support for the notion that genetically rearranged cell populations are part of the OA process.

Aged↗

PubMed1998

Polyclonal expansion of cells with trisomy 7 in synovia from patients with osteoarthritis.

Trisomy 7 as the single chromosome aberration has been found in a variety of neoplasms and in normal tissue in the proximity of tumors, as well as in non-neoplastic lesions. Recently, we described a nonrandom pattern of chromosome aberrations, in particular, a gain of chromosome 7, in synovia, cartilage, and osteophytes from patients with osteoarthritis. To study the clonal origin of trisomy 7 in osteoarthritis, multiple synovial samples were collected from five women, all of whom were informative heterozygotes with regard to the X-linked human androgen receptor gene (AR). From each case, three to four independent cell cultures were initiated. Trisomic cell populations were subcloned from the individual cultures, and it was established whether or not the same allele of AR was inactivated in trisomic cells from different parts of the same joint. The finding of a polyclonal X-inactivation pattern in two of the cases provides strong evidence that gain of an extra copy of chromosome 7 occurs independently in multiple cells.

Aged↗

PubMed1997

Clonal chromosome aberrations are present in vivo in synovia and osteophytes from patients with osteoarthritis.

We have previously reported recurrent clonal chromosomal aberrations in synovia, osteophytes and articular cartilage from patients with osteoarthritis (OA). In particular, gain of chromosomes 5 and 7 was found to be strongly associated with OA. In order to exclude the possibility of in vitro artefacts, we studied three to four parallel, independent cultures from ten samples of synovia and three samples of osteophytes from ten women with primary OA. In all, 40 cultures were cytogenetically analysed, 39 of which had clonal chromosomal aberrations. The most common aberrations were +7 and +5 which were found in 38 and 12 cultures, respectively. There were striking karyotype similarities among the parallel cultures from each case. Out of a total of 83 clones, only 11 were unique for one culture, 7 from synovia and 4 from osteophytes. The genetic homogeneity among different cultures from the same patients excludes the possibility of in vitro artefacts and indicates a widespread distribution of the cytogenetically aberrant clones in vivo.

Aged↗