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Y Ino

Publications and source records attributed to Y Ino.

At least 19 recordsLinked to original sources
PubMed2001

PTEN is a target of chromosome 10q loss in anaplastic oligodendrogliomas and PTEN alterations are associated with poor prognosis.

Allelic loss of 10q is a common genetic event in malignant gliomas, with three 10q tumor suppressor genes, ERCC6, PTEN, and DMBT1, putatively implicated in the most common type of malignant glioma, glioblastoma. Anaplastic oligodendroglioma, another type of malignant glioma, provides a unique opportunity to study the relevance of particular genetic alterations to chemosensitivity and survival. We therefore analyzed these three genes in 72 anaplastic oligodendrogliomas. Deletion mapping demonstrated 10q loss in 14 of 67 informative cases, with the PTEN and DMBT1 regions involved in all deletions but with the ERCC6 locus spared in two cases. Seven tumors had PTEN gene alterations; two had homozygous DMBT1 deletions, but at least one reflected unmasking of a germline DMBT1 deletion. No mutations were found in ERCC6 exon 2. Chemotherapeutic response occurred in two of the seven tumors with PTEN alterations, but with unexpected short survival times. PTEN gene alterations were not associated with poor therapeutic response in multivariate analysis, but were independently predictive of poor prognosis even after multivariate adjustment for both 10q and 1p loss. In anaplastic oligodendroglioma, therefore, PTEN is a target of 10q loss, and PTEN alterations are associated with poor prognosis, even in chemosensitive cases.

Agglutinins↗
PubMed2001

Involvement of c-Src in carcinoma cell motility and metastasis.

Carcinoma cells exhibit dysfunction / dysregulation of cell adhesion systems that correlates with their abilities to migrate, invade, and metastasize. Here we show that the tyrosine kinase c-Src is required for motility and metastasis of two carcinoma cell lines. Adherent KYN-2 cells having a high level of c-Src kinase activity become scattered, extend lamellipodia, and exhibit high motility. Expression of a dominant-negative mutant form of c-Src caused formation of stress fibers and focal adhesions, and markedly reduced motility. HCT15 cells extended lamellipodia and became scattered in response to lysophosphatidic acid stimulation in parallel with transient activation of c-Src, which was inhibited by expression of a dominant-negative mutant form of c-Src or treatment with a specific Src kinase inhibitor. Furthermore, implantation of dominant-negative c-Src transfectants into the peritoneal cavity of SCID mice resulted in reduced peritoneal dissemination compared with control transfectants. These findings indicate that c-Src activation is critically involved in carcinoma cell migration and metastasis.

Adenocarcinoma↗
PubMed2001

Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis.

PURPOSE: In a prior study of anaplastic oligodendrogliomas treated with chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of chromosome 1p correlated with better chemotherapeutic response and overall survival. However, in this group of patients in whom therapeutic management was not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all patients whose tumors harbor a 1p loss have long survival. EXPERIMENTAL DESIGN: To clarify the clinical relevance of molecular genetic testing at the time of diagnosis for patients with anaplastic oligodendrogliomas, we studied a larger, more homogeneous group of 50 patients with histologically defined anaplastic oligodendrogliomas treated with a chemotherapeutic regimen as the principal initial therapy. RESULTS: We demonstrate that these tumors can be divided genetically into four therapeutically and prognostically relevant subgroups. Patients whose tumors have combined but isolated losses of 1p and 19q have marked and durable responses to chemotherapy associated with long survival, with or without postoperative radiation therapy. Other tumors with chromosome 1p alterations also respond to chemotherapy, but with shorter duration of response and patient survival. Tumors lacking 1p loss can also be divided into two subgroups: those with TP53 mutations, which may also respond to chemotherapy but recur quickly, and those without TP53 mutations, which are poorly responsive, aggressive tumors that are clinically and genotypically similar to glioblastomas. CONCLUSIONS: These data raise the possibility, for the first time, that therapeutic decisions at the time of diagnosis might be tailored to particular genetic subtypes of anaplastic oligodendroglioma.

Adolescent↗
PubMed2000

Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas.

INTRODUCTION: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. MATERIALS AND METHODS: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. RESULTS: Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome lp loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004). CONCLUSION: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy +/- chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma.

Adolescent↗
PubMed2000

Inhibitory effects of newly synthesized active center-directed trypsin-like serine protease inhibitors on the complement system.

OBJECTIVE: To obtain a synthetic anti-complement inhibitor which has stronger activity than FUT-175 (nafamostat mesilate), as a synthetic ester derivative containing amidino and guanidino groups. METHODS: We synthesized several modified compounds of FUT-175. The anti-complement activities were measured using synthetic substrates and complement-mediated hemolysis in vitro. The anti-complement activity in vivo was evaluated via Forssman systemic shock in guinea pigs. RESULTS: FUT-175 inhibited C1r and C1s with IC50s of 1.7x10(-6) and 3.2x10(-7) M, respectively. Inhibitory activities were decreased by substitution of the amidino group with a hydrogen atom (compound 2), but not the guanidino group with a hydrogen atom (compound 3). Compound 6, in which the benzene ring of compound 3 was substituted with a furan ring, inhibited C1r and the complement-mediated hemolysis in high-diluted serum with higher potency than FUT-175. The inhibitory activity of compound 6 in hemolysis was weakened in low diluted serum. Compound 7 had a guanidino group inserted into compound 6; however, Compound 7 strongly inhibited hemolysis even in low-diluted serum, and suppressed Forssman systemic shock more potently than both FUT-175 and compound 6. CONCLUSIONS: These data suggest that the 2-furylcarboxylic acid derivatives have a strong potential for inhibiting the activities of the complement, and the guanidino group was required to retain high inhibitory activities in vivo, and compound 7 is a hopeful anti-complement agent.

Animals↗
PubMed2000

Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma: prognostic significance of E2F-1 and p16INK4A.

In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data from our previous studies of CDKN2A deletion and hypermethylation, other p53 pathway components, p27Kip1 expression, and proliferation, as well as with clinical outcome, including prognosis. We found aberrant pRb expression in four (12%) of 34 DLCLs. One of these had a point mutation in intron 3 10 bp downstream of exon 3 generating a novel splice signal. Seven tumours (21%) showed cyclin D3 overexpression, including all three thyroid lymphomas (P = 0.006). Cyclin D3 overexpression and p16INK4A/pRb aberrations were mutually exclusive, supporting an oncogenic role for cyclin D3 in DLCL. p16INK4A inactivation, cyclin D3 overexpression, or aberrant pRb expression was identified in 18 of 34 DLCLs (53%). Combining these results with our previous p53 pathway studies showed that 82% of the de novo DLCLs had alterations of these pathways, and that both pathways were altered in 13 cases (38%). Low E2F-1 expression was associated with treatment failure (P = 0.020), and multivariate analysis of overall survival identified both low E2F-1 expression (relative risk = 6.9; P = 0.0037) and p16INK4A inactivation (relative risk = 3.3; P = 0.0247) as independent prognostic markers. These data support a role of E2F-1 as tumour suppressor gene in lymphoma and strongly suggest that the RB1 and p53 pathways are important in the development of de novo DLCL. Furthermore, low E2F-1 expression and p16INK4A inactivation may serve as prognostic markers for patients with this type of lymphoma.

Antigens, Nuclear↗
PubMed2000

Molecular genetics of radiographically defined de novo glioblastoma multiforme.

Glioblastoma multiforme (GBM) represents the final endpoint of anaplastic progression in astrocytomas. GBM which arise without clinical evidence of a prior low-grade astrocytoma (LGA) have been designated de novo GBM, and are thought to develop rapidly from initial tumour formation. However, a purely clinical definition of de novo GBM does not exclude a long-standing, asymptomatic low-grade tumour. This study therefore sought to determine the genetic features of a unique group of cases in which GBMs were documented to have arisen radiographically in defined period of time (radiographically defined de novo GBM). Clinical and genetic features were examined in a group of 11 patients with a histological diagnosis of high-grade astrocytoma at first biopsy and radiographically defined de novo GBM. The mean age of the patients at tumour diagnosis was 62 years (range 32-87). Six of 11 tumours arose in the temporal lobes. Eight of 11 tumours had epidermal growth factor receptor (EGFR) overexpression, and EGFR gene amplification was found in five of the six analysed cases. Overexpression of p53 was observed in only one tumour, and a TP53 mutation was present in this case. p16 immunostaining was undetectable in 10 cases, and homozygous deletion of CDKN2A was observed in four of the six studied tumours. pRb expression was lost in four tumours. Mutations in the PTEN gene were detected in two of six cases. The results in this unique group of cases confirms the prior hypothesis that the profile of genetic alterations in de novo GBM is distinct from that of GBM arising from a known LGA, and that these specific genetic pathways promote the rapid development of GBM.

Adult↗
PubMed2000

Primary lymphoma of peripheral nerve: report of four cases.

Lymphoma presenting as a solitary tumor of peripheral nerve is exceedingly rare, with only six previously reported cases. The authors describe an additional four cases of primary lymphoma of peripheral nerve involving the sciatic nerve (two cases), the radial nerve, and the sympathetic chain and spinal nerve. The patients were two men and two women with an average age of 55.5 years. All tumors were high-grade B-cell lymphomas. Two patients experienced relapse of disease with involvement of other nervous system sites and died of lymphoma. One patient is alive with stable local disease at 57 months. The fourth patient is alive with no evidence of disease at 54 months. Expression of neural cell adhesion molecule (CD56) has been reported to correlate with an increased incidence of central nervous system involvement in peripheral T-cell lymphoma; all their cases were CD56 negative. Recent reports indicate a high proportion of primary brain lymphomas show loss of CDKN2A/p16 gene expression. Therefore, CDKN2A/p16 was evaluated in their patients both by polymerase chain reaction and by immunohistochemistry for the p16 protein. The authors found homozygous deletion of the CDKN2A/p16 gene in one of three patients studied, confirmed immunohistochemically by absent staining for p16. The fourth patient showed absent staining for p16, suggesting inactivation of the gene in this case as well. The two patients with p16 loss both died of lymphoma, whereas the two patients with normal p16 expression are alive. Primary lymphoma of peripheral nerve is a rare neoplasm, usually of large B-cell type, has a variable prognosis, and appears to have less consistent loss of p16 expression than primary central nervous system lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics.

Normal human cells exhibit a limited replicative life span in culture, eventually arresting growth by a process termed senescence. Progressive telomere shortening appears to trigger senescence in normal human fibroblasts and retinal pigment epithelial cells, as ectopic expression of the telomerase catalytic subunit, hTERT, immortalizes these cell types directly. Telomerase expression alone is insufficient to enable certain other cell types to evade senescence, however. Such cells, including keratinocytes and mammary epithelial cells, appear to require loss of the pRB/p16(INK4a) cell cycle control mechanism in addition to hTERT expression to achieve immortality. To investigate the relationships among telomerase activity, cell cycle control, senescence, and differentiation, we expressed hTERT in two epithelial cell types, keratinocytes and mesothelial cells, and determined the effect on proliferation potential and on the function of cell-type-specific growth control and differentiation systems. Ectopic hTERT expression immortalized normal mesothelial cells and a premalignant, p16(INK4a)-negative keratinocyte line. In contrast, when four keratinocyte strains cultured from normal tissue were transduced to express hTERT, they were incompletely rescued from senescence. After reaching the population doubling limit of their parent cell strains, hTERT(+) keratinocytes entered a slow growth phase of indefinite length, from which rare, rapidly dividing immortal cells emerged. These immortal cell lines frequently had sustained deletions of the CDK2NA/INK4A locus or otherwise were deficient in p16(INK4a) expression. They nevertheless typically retained other keratinocyte growth controls and differentiated normally in culture and in xenografts. Thus, keratinocyte replicative potential is limited by a p16(INK4a)-dependent mechanism, the activation of which can occur independent of telomere length. Abrogation of this mechanism together with telomerase expression immortalizes keratinocytes without affecting other major growth control or differentiation systems.

Cell Differentiation↗
PubMed2000

Involvement of eosinophils in the early-phase allergic reaction in a guinea pig rhinitis model.

BACKGROUND: Eosinophils are found in the nasal lavage fluid (NLF) and nasal biopsies of patients with allergic rhinitis after a nasal antigen challenge, and associated not only with a late-phase allergic reaction (LPR) but also an early phase allergic reaction (EPR). Numerous studies have been carried out to clarify the participation of eosinophils in LPR or airway hyperresponsiveness. However, there has been no published report describing in detail the role of eosinophils during EPR. To better understand the involvement of eosinophils in EPR, we studied the effects of repeated antigen challenges on nasal airway responsiveness and eosinophilic inflammation in EPR using a guinea pig rhinitis model. METHODS: Nasal airway responsiveness was measured as the nasal airway resistance (NAR) after nasal antigen provocation. Eosinophilic inflammation during EPR was assessed by nasal lavage and histopathological examination using two groups of animals: those in group 1 were subjected to a sensitization pretreatment only, and those in group 2 were subjected to a pretreatment of sensitization followed by repeated nasal challenges. RESULTS: Repeated antigen challenges induced nasal hyperresponsiveness as indicated by a decrease in the antigen provocation dose and a significant increase in NAR. Furthermore, significant increases in eosinophil counts, eosinophil peroxidase (EPO) activity and protein content in NLF during EPR were observed following antigen provocation in group 2. There were significant correlations between the levels of these parameters, and albumin was the most prevalent of the proteins in NLF. Histopathological examination showed that the degree of eosinophil infiltration into the lamina propria of the nasal mucosa of the animals in group 2 was significantly and apparently higher than in group 1. Particularly, epithelial disruption and mucosal edema were significantly elevated after antigen provocation in group 2. CONCLUSIONS: These results suggest that chronic eosinophil accumulation is induced by repeated antigen challenges in the nasal tissue, and that once antigen provocation occurs, eosinophils in the tissue are activated and responsible for the amplification of EPR such as vascular permeability and mucosal edema.

Animals↗
PubMed2000

Long survival and therapeutic responses in patients with histologically disparate high-grade gliomas demonstrating chromosome 1p loss.

OBJECT: Allelic loss of chromosome 1p is a powerful predictor of tumor chemosensitivity and prolonged survival in patients with anaplastic oligodendrogliomas. Chromosome 1p loss also occurs in astrocytic and oligoastrocytic gliomas, although less commonly than in pure oligodendroglial tumors. This observation raises the possibility investigated in this study that chromosome 1p loss might also provide prognostic information for patients with high-grade gliomas with astrocytic components. METHODS: The authors report on seven patients with high-grade gliomas composed of either pure astrocytic or mixed astrocytic-oligodendroglial phenotypes, who had remarkable neuroradiological responses to therapy or unexpectedly long survivals. All of the tumors from these seven patients demonstrated chromosome 1p loss, whereas other genetic alterations characteristic of high-grade gliomas (p53 gene mutations, EGFR gene amplification, chromosome 10 loss, chromosome 19q loss, or CDKN2A/p16 deletions) were only found in occasional cases. The authors also assessed the frequency of chromosome 1p loss in a series of anonymous high-grade astrocytoma samples obtained from a tumor bank and demonstrate that this genetic change is uncommon, occurring in only 10% of cases. CONCLUSIONS: Although any prognostic importance of chromosome 1p loss in astrocytic or mixed astrocytic-oligodendroglial gliomas can only be determined in larger and prospective series, these findings raise the possibility that some high-grade gliomas with chromosome 1p loss, in addition to pure anaplastic oligodendrogliomas, may follow a more favorable clinical course.

Adult↗
PubMed1999

Clinocopathologic significance of laminin-5 gamma2 chain expression in squamous cell carcinoma of the tongue: immunohistochemical analysis of 67 lesions.

BACKGROUND: The laminin-5 gamma2 chain plays an important role in cell migration during tumor invasion and tissue remodeling. METHODS: Laminin-5 gamma2 chain expression in squamous cell carcinomas of the tongue in 67 patients with Stage II, III, or IVA,B (excluding the cases with distant metastasis) was examined immunohistochemically to determine its associations with the clinicopathologic features of each tumor. The predominant staining patterns were categorized as follows: A, few or no tumor cells were positive; B, part of the tumor nest periphery was positive; C, the tumor nest periphery was circumferentially positive; or D, almost all the tumor cells were positive. RESULTS: Laminin-5 gamma2 chain expression was observed clearly in tumor cell cytoplasm. Of the 67 tumors examined, 6 (9%), 31 (46%), 19 (28%), and 11 (17%) showed staining patterns A, B, C, and D, respectively. With progression from staining pattern A to D, the number of immunopositive tumor cells increased significantly (P<0.0001), and the tumor histology showed significantly more infiltrative growth (P<0.0001) and poorer differentiation (P = 0.0021). Furthermore, both univariate (P = 0.0019) and multivariate (P = 0.0003; hazard ratio = 3.132) analysis of the patients' survival revealed that the prognosis became significantly poorer with progression from staining pattern A to D. CONCLUSIONS: Increased laminin-5 gamma2 chain immunoreactivity, which may reflect a high invasive potential of cancer cells, is a factor indicative of a poor prognosis for patients with squamous cell carcinoma of the tongue.

Adult↗
PubMed1999

Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation.

Patients with neurofibromatosis 1 (NF1) are predisposed to develop multiple neurofibromas (NFs) and are at risk for transformation of NFs to malignant peripheral nerve sheath tumors (MPNSTs). Little is known, however, about the biological events involved in the malignant transformation of NFs. We examined the CDKN2A/p16 gene and p16 protein in NFs and MPNSTs from patients with NF1. On immunohistochemical analysis, all NFs expressed p16 protein. The MPNSTs, however, were essentially immunonegative for p16, with striking transitions in cases that contained both benign and malignant elements. None of the benign tumors had CDKN2A/p16 deletions, whereas three of six MPNSTs appeared to have homozygous CDKN2A/p16 deletions. Methylation analysis and mutation analysis of CDKN2A/p16 in MPNSTs did not reveal any abnormalities. These results show that malignant transformation of NF is associated with loss of p16 expression, which is often secondary to homozygous deletion of the CDKN2A/p16 gene. The findings suggest that CDKN2A/p16 inactivation occurs during the malignant transformation of NFs in NF1 patients and raises the possibility that p16 immunohistochemistry may provide ancillary information in the distinction of NF from MPNST.

Adolescent↗
PubMed1999

Mapping of a target region of allelic loss to a 0.5-cM interval on chromosome 22q13 in human colorectal cancer.

BACKGROUND & AIMS: Chromosomal allelic losses have a varying frequency in colorectal cancer. The aim of this study was to define the target region of allelic loss on chromosome 22q in human colorectal carcinogenesis. METHODS: Fifty-seven pairs of matched normal colonic mucosa and tumor specimens from patients with colorectal cancer, as well as 15 colon cancer-derived cell lines, were genotyped using 15 microsatellite markers spanning chromosome 22q. A potential candidate gene was analyzed by a single-strand conformation polymorphism (SSCP)/direct DNA sequencing approach. RESULTS: After excluding 7 tumors with evidence of microsatellite instability, allelic loss was observed in 11 of the informative tumors (22%), 5 of which exhibited losses in all informative loci. The remaining 6 tumors showed variable patterns of partial allelic loss on chromosome 22q, thereby localizing a minimal region of allelic deletion between markers D22S1171 and D22S928. Physical mapping showed that this interval was 0.57 cM consisting of approximately 425 kilobases. Database searches identified the NBK/BIK gene, a proapoptotic BCL-2 family member, as a candidate gene in that region. However, SSCP/sequencing analysis excluded mutations of this gene. CONCLUSIONS: This study provides evidence for the involvement of putative tumor-suppressor gene(s) on chromosome 22q in human colorectal carcinogenesis. The identification of a 0.5-cM interval serves as the basis for the isolation of such a gene by positional cloning.

Alleles↗
PubMed1999

Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma.

The two gene products of the CDKN2A gene, p16 and p19ARF, have recently been linked to each of two major tumour suppressor pathways in human carcinogenesis, the RB1 pathway and the p53 pathway. p16 inhibits the phosphorylation of the retinoblastoma gene product by cyclin D-dependent kinases, whereas p19ARF targets MDM2, a p53 inhibitory protein, for degradation. A deletion of CDKN2A would therefore disturb both pathways. To explore the p53 pathway genes as a functional unit in diffuse large B cell non-Hodgkin's lymphomas (DLCL), we wanted to see whether there exists mutually exclusiveness of aberrations of CDKN2A, MDM2 and p53, since this has not been analysed previously. We investigated 37 DLCL for aberrations of p15, p16, p19ARF, MDM2, and p53 at the epigenetic, genetic and/or protein levels. Homozygous deletion of CDKN2A was detected in seven (19%) of 37 tumours, and another three cases were hypermethylated at the 5' CpG island of p16. No point mutations were found in CDKN2B or CDKN2A. Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue for p16 confirmed these results, as all tumours with alterations of CDKN2A were p16 immunonegative. We found p53 mutations in eight (22%) cases and MDM2 overexpression in 16 (43%) tumours. Twenty-three (62%) tumours had alterations of one or more p53 pathway components (p53, p19ARF and MDM2). Furthermore, 7/9 (78%) p16-immunonegative tumours showed co-aberration of p53 and/or MDM2. The lack of correlation between these aberrations suggests that DLCL acquire additional growth advantage by inactivating both of these critical regulatory pathways.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1999

Common regions of deletion on chromosome 22q12.3-q13.1 and 22q13.2 in human astrocytomas appear related to malignancy grade.

Approximately 30% of human astrocytomas have been reported to display allelic loss of the long arm of chromosome 22, suggesting the presence of a chromosome 22q astrocytoma suppressor gene. To define the most likely location for this putative tumor suppressor, we performed deletion mapping on 141 tumors using 16 chromosome 22q microsatellite markers. Allelic loss of 22q was observed in 2/12 (17%) of astrocytomas, 9/29 (31%) of anaplastic astrocytomas, and 38/100 (38%) of glioblastomas, consistent with a role for chromosome 22q loss in astrocytoma progression as well as formation. Twenty-two tumors exhibited allelic loss at every informative locus, consistent with loss of the entire arm of 22q. Twenty-seven tumors showed partial deletions, with one common region of deletion at 22q12.3-q13.1 between markers D22S280 and D22S282, and a second candidate region at 22q13.2 near the marker D22S1170. For the proximal candidate region, the incidence of allelic loss was similar between grades; for the distal locus, the incidence increased with grade, raising the possibility that the distal locus is involved in a later stage of astrocytoma tumorigenesis.

Alleles↗