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Maija Tarkkanen

Publications and source records attributed to Maija Tarkkanen.

7 recordsLinked to original sources
PubMed2006

Malignant fibrous histiocytoma of bone: analysis of genomic imbalances by comparative genomic hybridisation and C-MYC expression by immunohistochemistry.

Malignant fibrous histiocytoma (MFH) of bone is a rare, highly malignant tumour. As very little is known about its genetic alterations, 26 bone MFHs were analysed by comparative genomic hybridisation (CGH). Twenty-three tumours (89%) had DNA sequence copy number changes (mean, 7.2 changes per sample). Gains were more frequent than losses (gains:losses=2.5:1). Minimal common regions for the most frequent gains were 8q21.3-qter (35%), 9q32-qter (35%), 7q22-q31 (35%), 1q21-q23 (31%), 7p12-pter (31%), 7cen-q11.2 (31%) and 15q21 (31%). Minimal common regions for the most frequent losses were 13q21-q22 (42%) and 18q12-q22 (27%). High-level amplifications were detected in 8 out of the 26 tumours (31%). The only recurrent amplifications, 1q21-q23 and 8q21.2-q22, were present in two samples (8%). As copy number increase at 8q24 (the locus of C-MYC) was frequent, the expression of C-MYC was studied by immunohistochemistry. Increased levels of c-myc protein were detected in 7 out of 21 tumours studied (33%). 81% of the samples studied both by CGH and immunohistochemistry showed concordant results. Furthermore, the findings of the present study were compared to previous publications on osteosarcoma, soft tissue MFH and fibrosarcoma of bone. Clear differences were detected in CGH aberration patterns, further supporting the concept of bone MFH as an individual bone tumour entity. Finally, the findings of the present study reflect well the high malignancy and aggressive nature of bone MFH.

Adolescent↗
PubMed2006

Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.

BACKGROUND: We compared docetaxel with vinorelbine for the adjuvant treatment of early breast cancer. Women with tumors that overexpressed HER2/neu were also assigned to receive concomitant treatment with trastuzumab or no such treatment. METHODS: We randomly assigned 1010 women with axillary-node-positive or high-risk node-negative cancer to receive three cycles of docetaxel or vinorelbine, followed by (in both groups) three cycles of fluorouracil, epirubicin, and cyclophosphamide. The 232 women whose tumors had an amplified HER2/neu gene were further assigned to receive or not to receive nine weekly trastuzumab infusions. The primary end point was recurrence-free survival. RESULTS: Recurrence-free survival at three years was better with docetaxel than with vinorelbine (91 percent vs. 86 percent; hazard ratio for recurrence or death, 0.58; 95 percent confidence interval, 0.40 to 0.85; P=0.005), but overall survival did not differ between the groups (P=0.15). Within the subgroup of patients who had HER2/neu-positive cancer, those who received trastuzumab had better three-year recurrence-free survival than those who did not receive the antibody (89 percent vs. 78 percent; hazard ratio for recurrence or death, 0.42; 95 percent confidence interval, 0.21 to 0.83; P=0.01). Docetaxel was associated with more adverse effects than was vinorelbine. Trastuzumab was not associated with decreased left ventricular ejection fraction or cardiac failure. CONCLUSIONS: Adjuvant treatment with docetaxel, as compared with vinorelbine, improves recurrence-free survival in women with early breast cancer. A short course of trastuzumab administered concomitantly with docetaxel or vinorelbine is effective in women with breast cancer who have an amplified HER2/neu gene. (International Standard Randomised Controlled Trial number, ISRCTN76560285.).

Analysis of Variance↗
PubMed2005

Gene amplifications in osteosarcoma-CGH microarray analysis.

Little is known about the genomic alterations underlying osteosarcoma. We performed a genomewide high-resolution gene copy number analysis of 22 osteosarcoma samples using comparative genomic hybridization on a cDNA microarray that contained cDNA clones of about 13,000 genes. Nineteen of the 22 cases had amplifications that on average spanned more than 1 Mb and contained more than 10 genes. Numerous regions of gain and loss were identified, and their boundaries were defined at high resolution. Novel amplicons were found at 14q11, 17q25, and 22q11-q13. Earlier-known large amplified regions were detected at 12q11-q15, 8q24, 6p12-p13, and 17p11-p13 in 8, 6, 5, and 4 of the 22 samples, respectively. Amplification of 12q was observed more frequently (36% of the cases) than previously reported. Previously known small amplicons at 1p34-p36, 1q21, 19q13, and 21q22 were seen in at least three cases. Our results implicate TOM1L2 and CYP27B1 as having roles as novel targets for the 17p and 12q amplicons, respectively. Details (www.helsinki.fi/cmg) of the amplified genes in each amplicon provide valuable raw data for further in silico studies.

Adolescent↗
PubMed2004

Genetic analysis of fibrosarcoma of bone, a rare tumour entity closely related to osteosarcoma and malignant fibrous histiocytoma of bone.

Fibrosarcoma (FS) of bone is an extremely rare and genetically uncharacterised malignant tumour arising in the skeleton. On the basis of clinicopathologic features it appears to be closely related to either fibroblastic osteosarcoma (OS) or malignant fibrous histiocytoma (MFH) of bone. In this study, 27 decalcified, paraffin-embedded FS of bone were collected for genetic and immunohistochemical characterisation. Good quality DNA, suitable for genetic analyses, was isolated from nine cases (7 primary tumours, 1 local recurrence, and 1 lung metastasis), which were analysed by comparative genomic hybridisation (CGH) on chromosomes and DNA microarrays. DNA sequence copy number changes were found in five out of seven primary tumours (72%), as well as in both, the local recurrence and the metastatic lesion, by CGH on chromosomes. The most frequent aberration was gain of the chromosomal region 22q, which was present in four out of the five primary tumours with genetic changes, in the local recurrence and, as the sole genetic aberration, in the lung metastasis. DNA microarray analysis showed that gain of the platelet-derived growth factor beta (PDGF-B) gene (located at 22q12.3-q13.1) was the most frequent gene imbalance, which was present in three out of the five analysed tumours. In these three cases, real-time PCR revealed a 2.1- to 2.7-fold increase of PDGF-B gene copy numbers. By immunohistochemistry, a positive reaction for B-chain-containing PDGF proteins was revealed in all the cases showing gain of 22q. A more extensive immunohistochemical analysis identified the presence of PDGF-B proteins in 8/20 primary FS of bone (40%), 3/3 lung metastases and in 1/2 local recurrences. A simultaneous positive reaction for PDGF-B proteins and PDGF receptors was found in two third of PDGF-B-positive cases (8/12). Taken together, the genetic and immunohistochemical data indicate that over-representation of the chromosomal region 22q, including particularly the PDGF-B gene, may be important for the pathogenesis of FS of bone. Our results also demonstrate that CGH on chromosomes and DNA microarrays are suitable for the genetic characterisation of decalcified, paraffin-embedded tumour tissue samples and may facilitate, combined with other techniques, the rapid acquisition of data providing insight into the molecular genetic and biologic basis of rare bone sarcomas. Moreover, these findings suggest the possible presence of an autocrine loop in FS of bone, which might be taken into account for planning innovative therapeutic strategies for patients unresponsive to conventional treatments.

Adult↗
PubMed2002

Positional cloning identifies a novel cyclophilin as a candidate amplified oncogene in 1q21.

Gains of 1q21-q23 have been associated with metastasis and chemotherapy response, particularly in bladder cancer, hepatocellular carcinomas and sarcomas. By positional cloning of amplified genes by yeast artificial chromosome-mediated cDNA capture using magnetic beads, we have identified three candidate genes (COAS1, -2 and -3) in the amplified region in sarcomas. COAS1 and -2 showed higher amplification levels than COAS3. Most notably, amplification was very common in osteosarcomas, where in particular COAS2 was highly expressed. COAS1 has multiple repeats and shows no homology to previously described genes, whereas COAS2 is a novel member of the cyclosporin-binding peptidyl-prolyl isomerase family, very similar to cyclophilin A. COAS2 was overexpressed almost exclusively in aggressive metastatic or chemotherapy resistant tumours. Although COAS2 was generally more amplified than COAS1, it was not expressed in well-differentiated liposarcomas, where amplification of this region is very common. All three genes were found to be amplified and over-expressed also in breast carcinomas. The complex nature of the 1q21-23 amplicons and close proximity of the genes make unequivocal determination of the gene responsible difficult. Quite likely, the different genes may give selective advantages to different subsets of tumours.

Amino Acid Sequence↗
PubMed2002

Amplification of 17p11.2 approximately p12, including PMP22, TOP3A, and MAPK7, in high-grade osteosarcoma.

Amplification of region 17p11.2 approximately p12 has been found in 13%-29% of high-grade osteosarcomas, suggesting the presence of an oncogene or oncogenes that may contribute to their development. To determine the location of these putative oncogenes, we established 17p11.2 approximately p12 amplification profiles by semiquantitative PCR, using 15 microsatellite markers and seven candidate genes in 19 high-grade osteosarcomas. Most of the tumors displayed complex amplification profiles, with frequent involvement of marker D17S2041 in 17p12 and TOP3A in 17p11.2 and, in some cases, very high-level amplification of PMP22 and MAPK7 in 17p11.2. Our findings suggest that multiple amplification targets, including PMP22, TOP3A, and MAPK7 or genes close to these candidate oncogenes, may be present in 17p11.2 approximately p12 and thus contribute to osteosarcoma tumorigenesis.

Bone Neoplasms↗