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J Wennerberg

Publications and source records attributed to J Wennerberg.

At least 19 recordsLinked to original sources
PubMed1998

Cytogenetic and fluorescence in situ hybridization characterization of chromosome 1 rearrangements in head and neck carcinomas delineate a target region for deletions within 1p11-1p13.

Cytogenetic analyses have revealed structural rearrangements of chromosome 1 in a large fraction of head and neck carcinomas (HNCA). These aberrations frequently affect chromosomal band 1p13 and the centromeric region, the latter often in the form of isochromosome i(1q) and whole-arm translocations. To delineate the critical region involved in rearrangements of proximal 1p, we have undertaken a more precise breakpoint mapping in 13 HNCAs, using metaphase fluorescence in situ hybridization with 11 yeast artificial chromosome (YAC) clones spanning 1p. All of the tumors had chromosome 1 changes at G-banding analyses. Fluorescence in situ hybridization showed that in almost all of the cases, at least one copy of chromosome 1 was affected by centromeric rearrangement. By the use of YAC clones mapped to juxtacentromeric regions and a centromere-specific alpha-satellite probe, we detected variable breakpoints in the whole-arm translocations. At the cytogenetic level, 1p13 rearrangements were frequent. However, molecular breakpoints within this band varied among the HNCAs tested. The lack of consistently rearranged chromosome segments indicates that the pathogenetically important consequence of 1p rearrangements in HNCAs is loss and/or gain of genes outside the breakpoint regions. In an assessment of the genomic imbalances, partial or complete overrepresentation of 1q was seen in eight cases. Loss of 1p material was also identified in eight cases; and in four of them, the deleted segments were too small to be discovered by G-banding analysis. The minimal overlapping deleted region was in the interval between YAC 959C4 (band p11-p12) and the centromere (p10). Our findings indicate that a target region potentially harboring tumor suppressor gene(s) crucial for HNCA is located within chromosomal bands 1p11-p13.

Centromere↗
PubMed1998

Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden.

BACKGROUND: This case-referent study was conducted to elucidate the role of selected exogenous agents in the etiology of head and neck cancer. The factors studied were tobacco smoking, alcohol intake, the use of moist oral snuff, dietary factors, occupational exposures, and oral hygiene. In this first report, the authors discuss the impact of tobacco smoking, the use of oral snuff, and alcohol consumption. METHODS: The study base was approximately 2 million person-years at risk and consisted of Swedish males age 40-79 years living in 2 geographic regions during the years 1988-1990. A total of 605 cases were identified in the base, and 756 controls were selected by stratified random sampling from population registries covering the base. RESULTS: Among those who were tobacco smokers at the time of the study, the relative risk of head and neck cancer was 6.5% (95% confidence interval, 4.4-9.5%). After cessation of smoking, the risk gradually declined, and no excess risk was found after 20 years. The relative risk associated with alcohol consumption of 50 grams or more per day versus less than 10 grams per day was 5.5% (95% confidence interval, 3.1-9.6%). An almost multiplicative effect was found for tobacco smoking and alcohol consumption. CONCLUSIONS: Tobacco smoking and alcohol intake had a strong interactive effect on the risk of squamous cell carcinoma of the head and neck. Moderate alcohol intake (10-19 grams per day) had little or no effect among nonsmokers. No increased risk was found for the use of Swedish oral snuff.

Adult↗
PubMed1998

Complex karyotypes in flow cytometrically DNA-diploid squamous cell carcinomas of the head and neck.

In squamous cell carcinoma of the head and neck (SCCHN), DNA ploidy as determined by flow cytometry (FCM) has been found to yield prognostic information but only for tumours at oral sites. Cytogenetic findings have indicated complex karyotype to be a correlate of poor clinical outcome. In the present study, 73 SCCHN were investigated with the two techniques. Aneuploid cell populations were identified in 49 (67%) cases by FCM but in only 21 (29%) cases by cytogenetic analysis. The chromosome index (CI), calculated as the mean chromosome number divided by 46, was compared with the respective DNA index (DI) obtained by FCM in 15 tumours, non-diploid according to both techniques, DI being systematically 12% higher than CI in this subgroup. Eight (33%) of the 24 tumours diploid according to FCM had complex karyotypes, three of the tumours being cytogenetically hypodiploid, three diploid and two non-diploid. The findings in the present study may partly explain the low prognostic value of ploidy status as assessed by FCM that has been observed in SCCHN. In addition, we conclude that FCM yields information of the genetic changes that is too unspecific, and that cytogenetic analysis shows a high rate of unsuccessful investigations, thus diminishing the value of the two methods as prognostic factors in SCCHN.

Adult↗
PubMed1998

Cytogenetic and molecular genetic demonstration of polyclonality in an acinic cell carcinoma.

The paradigm that human malignancies are monoclonal has been questioned during recent years by the finding of unrelated, cytogenetically aberrant clones in short-term cultures from certain tumour types, notably carcinomas of the breast, skin and upper aerodigestive tract. In order to analyse whether cytogenetically unrelated clones are also unrelated at the molecular level, we analysed the X-chromosome inactivation status in cell cultures from a cytogenetically highly polyclonal acinic cell carcinoma of the parotid gland. By using cell cultures dominated by a single abnormal clone, obtained through in vitro culturing for 3-5 passages, we showed that the different clones must indeed have originated from different cells.

Aged↗
PubMed1998

p53 mutation, but not p53 overexpression, correlates with survival in head and neck squamous cell carcinoma.

Survival in squamous cell carcinoma of the head and neck (HNSCC) was compared with overexpression and mutation of the p53 gene. Archival tissue from 77 tumours was analysed for protein expression using immunohistochemistry (IHC) with the monoclonal antibody Do-7, and for the presence of mutation in exons 5-8 using single-stranded conformation polymorphism (SSCP), followed by DNA sequencing in SSCP-positive cases. p53 expression was scored as high (>70% nuclei stained) in 25 (32%) tumours, as intermediate (10-70% nuclei stained) in 19 (25%) tumours and as low (<10% nuclei stained) in 33 (43%) tumours. Twelve (18%) tumours exhibited gene mutation (ten missense and two nonsense mutations) and an additional five tumours contained changes that could not result in amino acid substitution or protein truncation. There was no correlation between gene expression and mutation, mutations being equally frequent in tumours with either high (4/25), intermediate (4/19) or low protein expression (4/33). Fifty-eight patients were eligible for survival analysis. There was a strong correlation between p53 mutation and cause-specific survival; median survival among mutated cases was 12.5 months compared with >160 months among non-mutated patients (P < 0.005). There was no correlation between p53 overexpression and survival. The results suggest that p53 mutation status is an important prognostic factor in HNSCC, and that IHC analysis of protein overexpression is an inadequate measure of gene mutation in these tumours.

Carcinoma, Squamous Cell↗
PubMed1998

FISH characterization of head and neck carcinomas reveals that amplification of band 11q13 is associated with deletion of distal 11q.

In order to characterize homogeneously staining regions (HSR) and other 11q13 rearrangements identified cytogenetically, we performed fluorescence in situ hybridization (FISH) using a CCND1 cosmid and five YAC clones spanning chromosomal bands 11q13-14 on metaphase cells from 14 primary and one metastatic head and neck carcinomas. At the cytogenetic level, a total of 17 HSR were detected in ten cases: five were in derivative chromosomes 11 in band 11q13, and 12 were located in other derivative chromosomes. Other forms of 11q13 rearrangements were observed in five cases, whereas two cases had normal chromosomes 11. FISH analysis demonstrated that all HSR but two were derived from the 11q13 band. The size of the amplicon varied from case to case, but the amplification always included the region covered by YAC 55G7, which contains the CCND1 locus. The amplification of CCND1 was confirmed by use of a CCND1 cosmid. We also showed that most of the cases (9 of 11) with 11q13 amplification had lost material from distal 11q. The breakpoints were mapped by FISH and were shown to cluster to the region between YACs 55G7 and 749G2. We conclude that loss of gene(s) in distal 11q may be as important as amplification of genes in 11q13 for the biological aggressiveness of head and neck carcinomas.

Adult↗
PubMed1997

Cytogenetic analysis of inverted nasal papillomas and demonstration of genetic convergence during in vitro passaging.

Three inverted nasal papillomas were cytogenetically investigated after short-term culture. Two of the cases were characterized by a single abnormal clone with t(1;8)(p36;q11) and trisomy 7, respectively, whereas the third papilloma showed extreme cytogenetic heterogeneity: of 852 analyzed cells, 329 belonged to 36 unrelated clones, 344 had non-clonal changes, and 179 had a normal chromosome constitution. The polyclonal papilloma was further analyzed during in vitro passage of 3 lines (L1-L3) cultured independently since initiation of the primary cultures and found to have 6, 16 and 6 unrelated clones at analysis of primary cultures. At passage 1, each line was further subdivided into 2 sub-lines (L1A and B, L2A and B, and L3A and B), which were cultured separately until the cells spontaneously stopped dividing. After 4 to 7 passages, each sub-line was dominated (83-98% of the cells) by a single clone. The cell populations that took over the cultures were the same within each set of sub-lines (A and B lines), demonstrating that clonal overgrowth in vitro is not random. The difference in clonal selection among the L1-L3 lines further shows that genetic convergence during in vitro growth in stable conditions is dependent not only on the clones' ability to adapt to the culture conditions, but also on the nature of the neighboring cells with which they collaborate and compete.

Aged↗
PubMed1997

Clonal chromosome aberrations accumulate with age in upper aerodigestive tract mucosa.

Short-term cultured non-neoplastic upper aerodigestive tract (UAT) mucosa samples from 36 patients with squamous cell carcinoma of the head and neck (SCC) and 53 patients with benign UAT disorders were cytogenetically analyzed. The cell cultures were divided into two series: in series A, cells were cultured in a medium stimulating outgrowth of mesenchymal cells; whereas the cultured cells in series B were of epithelial morphology. Series A was further subdivided into three different age groups (< or = 15 years, 16-59 years, and > or = 60 years) of non-SCC patients and one SCC group. Series B was composed of two groups; one with and one without SCC. Among the non-SCC patients in series A, there was an increase with age in the frequency of cells/sample with numerical and structural chromosomal changes as well as in the incidence of clonal chromosomal aberrations. No differences could, however, be detected between cancer patients and age-matched controls. In series B, the frequency of cells/sample with numerical changes and the incidence of clonal numerical aberrations were significantly higher among SCC patients. Three main conclusions could be drawn. First, the frequencies of clonal and non-clonal chromosome aberrations in UAT mucosa were age dependent. Second, the cytogenetic support for the validity of the field cancerization hypothesis was restricted to increased levels of numerical chromosome changes in epithelial cell cultures from cancer patients. Third, clonal chromosome aberrations, including autosomal and sex chromosome aneuploidies as well as structural rearrangements, are not restricted to neoplastic mucosal cells.

Adolescent↗
PubMed1997

Correlation between p53 mutation and cyclin D1 amplification in had and neck squamous cell carcinoma.

Mutations in the p53 tumour suppressor gene and amplification of the cyclin D1 (CCND1) oncogene have been commonly reported in various malignancies. In the present study of 39 squamous cell carcinomas of the head and neck, p53 mutations were manifest in 11 (28%) of the cases, whereas CCND1 amplification was seen in 6 (16%) of 37 analysed tumours. The 10 mutations occurring in coding sequences of p53 were found in exon 5 (4 cases), exon 6 (3 cases),f and exon 8 (3 cases). No mutation was found in exon 7. Eight of the 10 exon nucleotide substitutions were missense mutations and two were nonsense mutations. All six tumours with CCND1 amplification also had p53 mutations, while an additional five tumours manifested p53 mutations in the absence of CCND1 amplification. There was a statistically significant positive correlation between these two gene alterations. This raises the possibility that mutation of p53 precedes CCND1 amplification in carcinogenesis.

Adult↗
PubMed1997

Cancer of the nasopharynx in children and young adults in Scandinavia.

Reports have been published indicating an increase in the incidence of cancer in the head and neck, e.g. the tongue, in children and young adults under 40 years of age. In the present study the number of new cases of nasopharyngeal cancer in Scandinavia during the period 1958-1992 was reviewed in the respective national cancer registers. Altogether 3,675 patients were diagnosed with cancer of the nasopharynx. Of these, 371 or 10.1% were under 40 years of age at the time of diagnosis. Within this time period no increase was seen in the relative amount of young among nasopharynx cancer patients in Scandinavia. When considering the whole 35-year period the percentage of patients below 40 years varied between the countries from 7.5% to 18.3%. The majority of the cases in each country occurred in males, both among the young patients as well as in the older age groups. Malignant neoplasms of the nasopharynx are rare in Scandinavia. Both the relative and absolute amount of patients under 40 years of age at the time diagnosis was stable. No difference in the 5-year relative survival rates was seen between the patient group under 40 years when comparing it with all age groups combined.

Adult↗
PubMed1997

Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET.

The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.

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

Metoclopramide as a modulator of cisplatin: effects on pharmacokinetcs and cisplatin-DNA adducts in tumor and normal tissue.

The antiemetic drug metoclopramide (MCA) has previously been shown to cause DNA damage, to inhibit DNA repair and to enhance the effect of the chemotherapeutic agent cisplatin. Cisplatin acts by binding to DNA and thus forming cisplatin-DNA adducts. The present study was designed to investigate whether MCA affects the pharmacokinetics of cisplatin and the levels of cisplatin-DNA adducts in tumor and kidney. The effect on kidney is of special interest since cisplatin is highly nephrotoxic. Nude mice with xenografted squamous cell carcinoma where injected with cisplatin 5 mg/kg i.p. alone or in combination with MCA 2 mg/kp i.p. MCA was given 8 h after cisplatin. Total platinum was measured in serum and cisplatin-DNA adducts were analyzed in tumor and kidney with quantitative immunohistochemistry at 1, 9 and 24 h after cisplatin administration. The efficacy after treatment with cisplatin, MCA or cisplatin + MCA was studied in terms of tumor size measurements during 3 weeks following treatment and our previous observation that MCA enhances the cisplatin cytotoxicity was confirmed. The addition of MCA to cisplatin resulted in a slight increase in serum-platinum concentrations at 9 h and increased levels of adducts in tumors at 24 h. There was a tendency, however, not statistically significant, for increased adducts also in kidney. Thus, our findings may indicate that the sensitization of MCA on the cytotoxicity of cisplatin is mediated by increased formation, maybe accompanied by inhibited repair, of cisplatin-DNA adducts.

Animals↗
PubMed1996

Flow cytometry analysis of malignant tumors of the head and neck--differences between two methods in the recognition of aneuploidy.

DNA aneuploidy, which reflects changes in nuclear DNA-content, as determined cytometrically is a candidate prognostic factor in squamous cell carcinoma of the head and neck. The aim of this study was to compare two different preparation methods with respect to their use in detecting aneuploid tumor cell populations in malignant tumors of the head and neck. Fresh frozen tumor material was used. The methods compared were a multistep procedure (A) including fixation of cells and enzymatic treatment, and a one step procedure (B). Both include RNAse and the use of propidium iodide for DNA staining. Forty-seven percent of the tumors were non-diploid according to method A, and 29% according to method B, discordant findings being made in 15 tumors, only two of which were non-SCC. Defining a 'true non-diploid tumor' in this series as a tumor with a DNA index outside the range of diploidy detected either by method A or B, 59% (29/49) of the tumors were non-diploid. The sensitivity was 0.48 (14/29) for method B and 0.79 (23/29) for method A. The striking differences in accuracy between methods A and B emphasize the need of caution when new methods are introduced, and when results obtained with different methods are compared.

Analysis of Variance↗
PubMed1995

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.

Adult↗
PubMed1995

Karyotypic features of malignant tumors of the nasal cavity and paranasal sinuses.

Cytogenetic analysis of short-term cultures from 6 tumors of the nasal cavity and paranasal sinuses--one esthesioneuroblastoma, 2 adenocarcinomas and 3 squamous-cell carcinomas (SCC)--revealed clonal chromosome aberrations in all cases. The esthesioneuroblastoma had a complex hyperdiploid karyotype. None of the aberrations was similar to those previously described in short-term cultures or established cell lines from esthesioneuroblastomas. The 2 adenocarcinomas had complex karyotypic changes, which in both cases included rearrangements of bands 9p22 and 14q11. One SCC had 5 unrelated pseudodiploid clones, 1 displayed a highly complex karyotype, including rearrangement of band 11q13, and 1 had simple karyotypic changes with loss of 6q material and gain of 3q. These findings are similar to those described in head-and-neck SCC at other sites.

Adenocarcinoma↗
PubMed1995

Tetraploidization and progressive loss of 6q in a squamous cell carcinoma of the parotid gland.

Cytogenetic analysis of short-term cultures from a squamous cell carcinoma (SCC) of the parotid gland revealed one clone with loss of the Y chromosome only, as well as three related subclones: 91,XXYY,add(6)(q21), -11,t(11;22)(q13;q11),ins(15;?)(q22;?)[cp5+ ++]/91,XXYY,add (6)(q21), -11,add(11)(p11), ins(15;?)(q22;?),der(22)t(11;22)(p11;q11)[2]/91,XXYY,add(6)(q11), -11,add(11)(p11),ins(15;?)(q22;?),der(22) t(11;22)(p11;q11) [cp4]. The finding of only one copy of all structurally rearranged chromosomes in a near-tetraploid karyotype indicates that tetraploidization was an early event in tumorigenesis. Rearrangements, in particular deletions, of 6q have previously been associated with adenoid salivary gland malignancies. Our finding of progressive 6q loss with clonal evolution, combined with the fact that 6q deletions were also seen in the two previously reported SCCs of the salivary glands, indicate that loss of genetic information from this chromosome arm is characteristic for most types of salivary gland carcinomas, irrespective of their histologic differentiation.

Aged↗