J Gregory Cairncross

Publications (58)430.42 Total impact

• Article: Imaging molecular signatures in oligodendroglioma.

  J Gregory Cairncross
  Clinical Cancer Research 12/2004; 10(21):7109-11. · 7.74 Impact Factor
• Article: Imaging correlates of molecular signatures in oligodendrogliomas.

  Joseph F Megyesi, Edward Kachur, Donald H Lee, Magdalena C Zlatescu, Rebecca A Betensky, Peter A Forsyth, Yoshifumi Okada, Hikaru Sasaki, Masahiro Mizoguchi, David N Louis, J Gregory Cairncross
  [show abstract] [hide abstract]
  ABSTRACT: Molecular subsets of oligodendroglioma behave in biologically distinct ways. Their locations in the brain, rates of growth, and responses to therapy differ with their genotypes. Retrospectively, we inquired whether allelic loss of chromosomal arms 1p and 19q, an early molecular event and favorable prognostic marker in oligodendrogliomas, were reflected in their appearance on magnetic resonance imaging. Loss of 1p and 19q was associated with an indistinct border on T(1) images and mixed intensity signal on T(1) and T(2). Loss of 1p and 19q was also associated with paramagnetic susceptibility effect and with calcification, a common histopathological finding in oligodendrogliomas. These data encourage prospective evaluation of molecular alterations and magnetic resonance imaging characteristics of glial neoplasms.
  Clinical Cancer Research 08/2004; 10(13):4303-6. · 7.74 Impact Factor
• Article: High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma.

  Lauren E Abrey, Barrett H Childs, Nina Paleologos, Lynne Kaminer, Steven Rosenfeld, Donna Salzman, Jonathan L Finlay, Sharon Gardner, Kendra Peterson, Wendy Hu, [......], Robert Bayer, Peter Forsyth, Douglas Stewart, Anne M Smith, David R Macdonald, Susan Weaver, David A Ramsey, Stephen D Nimer, Lisa M DeAngelis, J Gregory Cairncross
  [show abstract] [hide abstract]
  ABSTRACT: Anaplastic oligodendroglioma is a chemosensitive glial neoplasm. To improve disease control and postpone cranial radiotherapy, we designed a phase II study of intensive procarbazine, lomunstine and vincristine followed by high-dose thiotepa with autologous stem cell rescue for patients with newly diagnosed anaplastic or aggressive oligodendroglioma. Sixty-nine patients with a median age of 42 (range: 18-67) and a median Karnofsky Performance Score of 90 (range: 70-100) were enrolled. Sixteen patients had a prior diagnosis of low-grade oligodendroglioma and 16 had mixed oligoastrocytoma pathology. Only patients with demonstrably chemosensitive enhancing tumors or those free of enhancing tumor after surgery and induction therapy were eligible to receive high-dose thiotepa. Thirty-nine patients (57%) completed the transplant regimen; their estimated median progression-free survival is 69 months and median overall survival has not been reached. Twelve transplanted patients (31%) relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with relapse; however, persistent non-enhancing tumor at transplant conferred an increased risk of relapse (p = 0.028). The transplant regimen was well-tolerated; median hospital stay was 20 days (range: 7-43) with a median time to ANC and platelet engraftment of 10 days. Thirty patients (43%) did not receive high-dose thiotepa because of stable or progressive disease (n = 21), excessive toxicity (n = 4), refusal of further therapy (n = 2), failure to obtain insurance coverage (n = 2), or other (n = 1). No treatment-related or long-term neurotoxicity was seen in the transplanted patients. High-dose chemotherapy with stem cell rescue as initial treatment for anaplastic oligodendroglioma is feasible and associated with prolonged tumor control in some patients.
  Journal of Neuro-Oncology 12/2003; 65(2):127-34. · 3.21 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Recent developments in the molecular characterization and treatment of oligodendroglial tumors.

  Martin van den Bent, Olivier-Louis Chinot, J Gregory Cairncross
  [show abstract] [hide abstract]
  ABSTRACT: Although many patients with oligodendrogliomas (ODs) and oligoastrocytomas (OAs) benefit from a combination of surgery and adjuvant radiotherapy, most patients eventually experience recurrence of their disease. Recent evidence has shown that ODs are more chemosensitive than other gliomas, including astrocytomas or glioblastoma multiforme. These initial findings have prompted further study of chemotherapy in treating ODs and mixed OAs. Advances in molecular genetic analysis have led to improvements in predicting response to chemotherapy and prognosis for ODs, OAs, and astrocytomas. Pure ODs are more chemosensitive than mixed ODs. This difference is related to different proportions of 1p/19q loss of heterozygosity in these neoplasms. Therefore, genetic analysis is likely to be key in determining appropriate treatment. The most common first-line chemotherapy for patients with OD is a procarbazine, lomustine, and vincristine (PCV) combination regimen. However, this regimen is associated with cumulative myelosuppression, nausea, vomiting, and weight loss. Therefore, other chemotherapy agents and regimens have been investigated. Perhaps the most promising is temozolomide, a novel alkylating agent that freely crosses the blood-brain barrier. Temozolomide is approved in the United States for the treatment of recurrent anaplastic astrocytomas and in Europe for any recurrent high-grade gliomas. Initial reports suggest that temozolomide is effective in treating ODs as first- and second-line chemotherapy. Unlike the PCV regimen, temozolomide is not associated with cumulative myelosuppression and is usually well tolerated. Further studies are needed to confirm the efficacy and safety profile of temozolomide and to determine the optimal dose and schedule for treating ODs.
  Neuro-Oncology 05/2003; 5(2):128-38. · 5.72 Impact Factor
• Article: Gene expression-based classification of malignant gliomas correlates better with survival than histological classification.

  Catherine L Nutt, D R Mani, Rebecca A Betensky, Pablo Tamayo, J Gregory Cairncross, Christine Ladd, Ute Pohl, Christian Hartmann, Margaret E McLaughlin, Tracy T Batchelor, Peter M Black, Andreas von Deimling, Scott L Pomeroy, Todd R Golub, David N Louis
  [show abstract] [hide abstract]
  ABSTRACT: In modern clinical neuro-oncology, histopathological diagnosis affects therapeutic decisions and prognostic estimation more than any other variable. Among high-grade gliomas, histologically classic glioblastomas and anaplastic oligodendrogliomas follow markedly different clinical courses. Unfortunately, many malignant gliomas are diagnostically challenging; these nonclassic lesions are difficult to classify by histological features, generating considerable interobserver variability and limited diagnostic reproducibility. The resulting tentative pathological diagnoses create significant clinical confusion. We investigated whether gene expression profiling, coupled with class prediction methodology, could be used to classify high-grade gliomas in a manner more objective, explicit, and consistent than standard pathology. Microarray analysis was used to determine the expression of approximately 12000 genes in a set of 50 gliomas, 28 glioblastomas and 22 anaplastic oligodendrogliomas. Supervised learning approaches were used to build a two-class prediction model based on a subset of 14 glioblastomas and 7 anaplastic oligodendrogliomas with classic histology. A 20-feature k-nearest neighbor model correctly classified 18 of the 21 classic cases in leave-one-out cross-validation when compared with pathological diagnoses. This model was then used to predict the classification of clinically common, histologically nonclassic samples. When tumors were classified according to pathology, the survival of patients with nonclassic glioblastoma and nonclassic anaplastic oligodendroglioma was not significantly different (P = 0.19). However, class distinctions according to the model were significantly associated with survival outcome (P = 0.05). This class prediction model was capable of classifying high-grade, nonclassic glial tumors objectively and reproducibly. Moreover, the model provided a more accurate predictor of prognosis in these nonclassic lesions than did pathological classification. These data suggest that class prediction models, based on defined molecular profiles, classify diagnostically challenging malignant gliomas in a manner that better correlates with clinical outcome than does standard pathology.
  Cancer Research 05/2003; 63(7):1602-7. · 7.86 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Analysis of a molecular genetic neuro-oncology study with partially biased selection.

  Rebecca A Betensky, David N Louis, J Gregory Cairncross
  [show abstract] [hide abstract]
  ABSTRACT: Oligodendrogliomas are a common variant of malignant brain tumors, and are unique for their relative sensitivity to chemotherapy and better prognosis. For these reasons, the identification of an objective oligodendroglial marker has been a long sought-after goal in the field of neuro-oncology. To this end, 75 patients who received chemotherapy at the London Regional Cancer Centre between 1984 and 1999 were studied (Ino et al., Clinical Cancer Research, 7, 839-845, 2001). Of these 75 patients, 50 were initially treated with chemotherapy (the current practice) and comprise a population-based sample. The remaining 25 patients were initially treated with radiation and were included in the study only because their tumor recurred, at which time they received chemotherapy. Because this group of 25 patients included neither those radiation patients whose tumors never recurred nor those radiation patients whose tumors recurred but were not treated with chemotherapy, issues of selection bias were of concern. For this reason, the initial analysis of these data included only the 50 population-based patients. This was unsatisfying given the rarity of this disease and of genetic information on this disease and led us to question whether we could undertake an analysis that includes all of the patients. Here we examine approaches for utilizing the entire study population, as well as the assumptions required for doing so. We illustrate that there are both costs and benefits to using the 25 selected patients.
  Biostatistics 05/2003; 4(2):167-78. · 2.14 Impact Factor
• Article: Acetazolamide therapy for symptomatic plateau waves in patients with brain tumors. Report of three cases.

  Christopher J Watling, J Gregory Cairncross
  [show abstract] [hide abstract]
  ABSTRACT: In this report, the authors describe three patients with malignant gliomas who experienced paroxysmal neurological symptoms triggered by standing. The symptoms were attributed to acute elevations of intracranial pressure, an uncommon phenomenon called "plateau waves." In each instance, the attacks occurred despite the fact that the patient was receiving dexamethasone therapy and stopped promptly with the addition of acetazolamide. Acetazolamide, an orally administered carbonic anhydrase inhibitor, appears to be a specific and effective therapy for this uncommon neurological disorder.
  Journal of Neurosurgery 08/2002; 97(1):224-6. · 2.96 Impact Factor
• Article: Influence of unrecognized molecular heterogeneity on randomized clinical trials.

  Rebecca A Betensky, David N Louis, J Gregory Cairncross
  [show abstract] [hide abstract]
  ABSTRACT: In solid tumor oncology, decisions regarding treatment and eligibility for trials are governed by histologic diagnosis. Despite this reliance on histology and the assumption that histology defines the disease, underlying molecular heterogeneity likely differentiates among patients' outcomes. To illustrate how unrecognized molecular heterogeneity might obscure a truly effective new therapy for cancer, we analyzed the planning assumptions and results of a hypothetical randomized controlled trial of chemoradiotherapy for a cancer found to be drug sensitive in preliminary phase II studies. Randomized controlled trials of effective cancer therapies can be falsely negative if therapeutic benefit is overestimated during study design because of enrichment of phase II trials for treatment-sensitive subtypes, a beneficial effect in responding patients is diluted by large numbers of nonresponding patients, or a beneficial effect in responders is reversed by a negative effect in nonresponders. Molecular heterogeneity, if it confers different risks to patients and is unaccounted for in the design of a randomized study, can result in a clinical trial that is underpowered and fails to detect a truly effective new therapy for cancer.
  Journal of Clinical Oncology 06/2002; 20(10):2495-9. · 18.37 Impact Factor
• Source

  Available from: Scott L Pomeroy

  Article: Focus on central nervous system neoplasia.

  David N Louis, Scott L Pomeroy, J Gregory Cairncross
  Cancer Cell 04/2002; 1(2):125-8. · 26.57 Impact Factor
• Article: DMBT1 polymorphisms: relationship to malignant glioma tumorigenesis.

  Hikaru Sasaki, Rebecca A Betensky, J Gregory Cairncross, David N Louis
  [show abstract] [hide abstract]
  ABSTRACT: The deleted in malignant brain tumors 1 (DMBT1) gene on 10q25-26 is a candidate tumor suppressor gene in malignant gliomas, but its role is controversial, e.g., some DMBT1 homozygous deletions reflect unmasking of constitutional deletion polymorphisms by 10q loss. To clarify the role of DMBT1 in gliomagenesis, we investigated three reported deletion hot spots. Homozygous deletions at DMBT1 repeat 2-4 to 2-7 were found in 10 of 73 gliomas with 10q loss, but all 10 deletions reflected unmasking of constitutional hemizygous deletions. Alleles bearing deletion 2-4/2-7 were not selected significantly for by 10q loss, with retention of only 10 of 16 deleted alleles. No homozygous deletion was detected at locus 74k in the 5' upstream region of DMBT1, and four tightly linked polymorphisms were found around this region; chromosome 10q loss randomly affected alleles with or without the variant sequences around locus 74k. Moreover, no significant selection pressure was detected for the haplotype with both deletion 2-4/2-7 and 5' polymorphisms. There was no segregation of deletion 2-4/2-7 in glioma patients compared with unrelated individuals from reference families but a suggestion of a difference in the distribution of the 5' polymorphisms between the reference individuals and glioma patients. Constitutional polymorphisms at DMBT1 repeat 2-9/2-10 appeared common in patients with both benign brain tumors and gliomas. A homozygote for both the 2-4/2-7 deletion and the 5' polymorphisms had a glioma arise at a typical age and without an apparent family cancer predisposition. These data suggest that DMBT1 polymorphisms are not likely primary targets of 10q loss in malignant gliomas and do not support a major role for DMBT1 in gliomagenesis.
  Cancer Research 04/2002; 62(6):1790-6. · 7.86 Impact Factor
• Article: The use of frailty hazard models for unrecognized heterogeneity that interacts with treatment: considerations of efficiency and power.

  Yi Li, Rebecca A Betensky, David N Louis, J Gregory Cairncross
  [show abstract] [hide abstract]
  ABSTRACT: Increasingly, genetic studies of tumors of the same histologic diagnosis are elucidating subtypes that are distinct with respect to clinical endpoints such as response to treatment and survival. This raises concerns about the efficiency of using the simple log-rank test for analysis of treatment effect on survival in studies of possibly heterogeneous tumors. Furthermore, such studies, designed under the assumption of homogeneity, may be severely underpowered. We derive analytic approximations for the asymptotic relative efficiency of the simple log-rank test relative to the optimally weighted log-rank test and for the power of the simple log-rank test when applied to subjects with unobserved heterogeneity, as reflected in a continuous frailty, that may interact with treatment. Numerical studies demonstrate that the simple log-rank test may be quite inefficient if the frailty interacts with treatment. Further, there may be a substantial loss of power in the presence of the frailty with or without an interaction with treatment.
  Biometrics 04/2002; 58(1):232-6. · 1.83 Impact Factor
• Article: A better way to find tumor in the CSF?

  Lisa M DeAngelis, J Gregory Cairncross
  Neurology 03/2002; 58(3):339-40. · 8.31 Impact Factor
• Article: Ki-67: a prognostic factor for low-grade glioma?

  Barbara J Fisher, Elitza Naumova, Christopher C Leighton, George N Naumov, Nancy Kerklviet, David Fortin, David R Macdonald, J Gregory Cairncross, Glenn S Bauman, Larry Stitt
  [show abstract] [hide abstract]
  ABSTRACT: Immunohistochemical techniques were used to detect the expression of Ki-67, a nuclear proliferation marker, in 180 low-grade glioma tumor specimens to determine whether Ki-67 is a prognostic predictor of survival or tumor recurrence. A clinical database of 180 low-grade glioma patients (35 children aged </=18 years and 145 adults) was compiled. Eighty patients had received postoperative radiotherapy (RT) and 100 patients had had RT deferred until the time of tumor progression/recurrence. Ki-67 indexes were evaluated retrospectively on tumor specimens from these patients using a semiautomated computer analysis technique. Ten observations were averaged per patient. The maximal Ki-67 value was recorded. The correlation between the Ki-67 index and survival was much higher for the averaged Ki-67 value than for the maximal value. Of the tumor specimens, 29% had a negative Ki-67 index (i.e., zero Ki-67 positive cells) and 7.7% had an average Ki-67 index of >/=5%. An average Ki-67 value of >/=5% was prognostically significant for reduced cause-specific survival (CSS, p = 0.05) and a Ki-67 level >/=10% was strongly significant of a poor survival outcome (p = 0.009). Ki-67 was not prognostically significant for progression-free survival. Other prognostically significant factors for CSS included age (p = 0.05), Karnofsky performance status (p = 0.0001), radiation dose (p = 0.02), extent of surgical resection (biopsy vs. others, p = 0.004), and timing of radiation (p = 0.0005). Ki-67 did not remain an independent statistically significant factor for CSS on multivariate analysis. Age and Ki-67 positivity (both maximal and average values) directly correlated (i.e., advancing age was associated with a higher Ki-67 index). When the patient group was further subdivided by age and timing of RT (postoperative vs. deferred), the prognostic significance of Ki-67 for CSS was lost. Within the deferred RT subgroup, a maximal Ki-67 >2% was associated with a worsened CSS. Within the pediatric population, Ki-67-negative patients had a 5-year CSS and progression-free survival of 100%. The 5-year CSS and progression-free survival declined significantly to 84% and 67% for patients with tumors demonstrating any degree of Ki-67 positivity (p = 0.005 and p = 0.006, respectively). Ki-67 is a useful predictor of CSS in low-grade gliomas; however, it is not independent of other prognostic factors, particularly age. Although Ki-67 was not helpful in predicting which adult patients were likely to benefit from postoperative RT, the results of the present study indicate a possible utility in the selection of pediatric patients for RT and in the selection of poorer prognosis patients for clinical trials.
  International Journal of Radiation OncologyBiologyPhysics 03/2002; 52(4):996-1001. · 4.11 Impact Factor
• Article: Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade "oligodendroglioma".

  Hikaru Sasaki, Magdalena C Zlatescu, Rebecca A Betensky, Loki B Johnk, Andrea N Cutone, J Gregory Cairncross, David N Louis
  [show abstract] [hide abstract]
  ABSTRACT: Allelic loss of chromosome 1p predicts increased chemosensitivity and better survival in oligodendroglial tumors. Clinical testing for 1p loss in oligodendroglial tumors at our hospital has allowed us to postulate that certain histological appearances are associated with 1p allelic status. Forty-four cases received for genetic testing were diagnosed by referring pathologists as pure low-grade oligodendroglioma. Central neuropathological review divided the series equally into 22 cases with classical oligodendroglioma histology and 22 with more astrocytic features. Molecular genetic analyses demonstrated 1p loss in 19 of 22 classic oligodendrogliomas (86%) and maintenance of both 1p alleles in 16 of 22 gliomas with astrocytic features (73%). No glial fibrillary acidic protein-positive cell type (gliofibrillary oligodendrocyte, minigemistocyte, cellular processes) was associated with 1p allelic status. Fourteen of the 44 cases were treated with chemotherapy at tumor progression: 3 "astrocytic" gliomas with 1p loss responded to PCV chemotherapy and 2 classic oligodendrogliomas that maintained both 1p alleles included a responder and a non-responder. These results suggest that histological appearance correctly predicts genotype in approximately 80% of low-grade gliomas, but that tumor genotype more closely predicts chemosensitivity. As a result, such objective molecular genetic analyses should be incorporated into patient management and into clinical trials of low-grade diffuse gliomas.
  Journal of Neuropathology and Experimental Neurology 02/2002; 61(1):58-63. · 4.26 Impact Factor
• Article: Phase II study of tiazofurin in gliomas in adults

  David J. Stewart, Elizabeth Eisenhauer, David R. Macdonald, J. Gregory Cairncross, Adrian Langleben
  [show abstract] [hide abstract]
  ABSTRACT: The National Cancer Institute of Canada conducted a Phase II study of tiazofurin 1100 to 1375 mg/m2 IV daily x 5 days in adults with grade 2, 3, and 4 gliomas. No responses were seen. Five of sixteen evaluable patients had stable disease for 38 to 147 days (median, 75 days). Treatment was generally well tolerated, and hence the dose was escalated from 1100mg/m2/day to 1375 mg/m2/day after the first twelve patients were entered. Treatment-induced hypertension requiring pharmacological intervention was seen in four patients. Gastrointestinal toxicity was generally mild. Treatment-related headache was seen in thirteen patients, and drowsiness or weakness was seen in seven patients.In summary, tiazofurin on this dose schedule does not have major activity against grade 2, 3, and 4 gliomas.
  Journal of Neuro-Oncology 01/1993; 15(2):175-179. · 3.21 Impact Factor
• Article: p53 Mutation, Expression, and DNA Ploidy in Evolving Gliomas: Evidence for Two Pathways of Progression

  Donald J. van Meyel, David A Ramsay, Alan G. Casson, Michael Keeney, Ann F Chambers, J Gregory Cairncross
  [show abstract] [hide abstract]
  ABSTRACT: Background Two lines of evidence indirectly implicate the tumor suppressor p53 (also known as TP53) gene in glioma development. First, germline mutations of the p53 gene are associated with increased susceptibility to glioma. Second, chromosome 17p deletions and p53 gene mutations are found frequently in suoradic gliomas of all malignancy stages. These observations suggest that mutations of the p53 gene may be early events in glioma development. Purpose Our purpose was to analyze 15 low-grade astrocytic gliomas that progressed to highergrade gliomas, examining the status of the p53 gene in both the initial and recurrent tumors. Also, we explored the relationships between p53 status, DNA ploidy, tumor grade, and patient survival. Methods Fifteen low-grade gliomas that recurred as tumors of higher grade 17–102 months after initial treatment (biopsy, resection, radiotherapy, or chemotherapy) were identified from hospital records of patients (eight male and seven female) aged 31–68 years. Pathologic diagnosis was re-evaluated. Polymerase chain reaction (PCR)-single-strand conformation polymorphism and DNA sequencing were perfomed on tissue samples from the initial and recurrent tumors of each patient, using oligonucleotide PCR primers directed to exons 5–9 of the p53 gene. p53 expression was determined by immunohistochemistry and DNA ploidy evaluated by DNA flow cytometry. Results Eight (53&percnt;) of fifteen tumors had p53 mutations in exons 5–9. Nine (64&percnt;) of fourteenwere immunopositive initially, and eight of these were also immunopositive at recurrence. p53 gene status was significantly associated with p53 expression in the initial tumor ( P &equals;.02), and p53 expression at initial diagnosis was significantly related to tumor pathology at recurrence ( P &equals;.03). Patients with p53 mutant tumors survived nearly twice as long as those without mutations (median survival, 61 versus 33 months; P &equals;.031). There was no significant difference in recurrence-free survival between patients with p53 mutant and nonmutant tumors (48 versus 33 months; P &equals;.37), but there was a significant difference in postrecurrence survival (17 versus 2 months; P &equals;.019). Conclusion Low-grade tumors that recurred as anaplastic gliomas were characterized by p53 gene mutation, immunopositivity, and DNA nondiploidy. Low-grade tumors that recurred as glioblastomas generally had intact p53 genes and were immunonegative. These findings suggest that histologically indistinguishable, low-grade astrocytic gliomas that are destined to progress to higher grades, do so along two distinct clinicopathologic pathways (either stepwise to anaplastic glioma, then glioblastoma, or directly to glioblastoma) marked by the presence or absence of p53 mutation. [J Natl Cancer Inst 86: 1011–1017, 1994]
• Article: Long-term survivors of glioblastoma: statistical aberration or important unrecognized molecular subtype?

  Donna Senger, J Gregory Cairncross, Peter A J Forsyth
  [show abstract] [hide abstract]
  ABSTRACT: Unlike most patients with glioblastoma multiforme who survive less than a year, approximately 2% have an unusually long survival after diagnosis and contemporary treatment (> or = 3 or more years); rarely, the disease appears to be "cured." Understanding these rare patients may tell us something important about the biology of glioblastoma multiforme. Patients who are young, have good performance status, and receive multimodalitytherapy (i.e., surgical resection, radiotherapy, and adjuvant chemotherapy) are more likely to have a long survival than older patients with poor performance status who are treated identically. However, the aforementioned clinical characteristics of long-term survivors do not explain why most patients with glioblastoma multiforme who have this same constellation of favorable features succumb to the disease relatively quickly. "Glioblastoma multiforme" is a group of diseases, one subtype of which behaves in a more indolent fashion, or responds well to current therapies, or both. In this review, we summarize the molecular characteristics of glioblastoma multiforme and pay special attention to molecular predictors of survival outcome, an area of research that is still in its infancy. We conclude by suggesting a translational research strategy that is aimed at uncovering the molecular signatures of long survivorship.
  The Cancer Journal 9(3):214-21. · 3.26 Impact Factor
• Article: Gliomas in families: Chromosomal analysis by comparative genomic hybridization

  Atul Patel, Donald J. van Meyel, Gayatry Mohapatra, Andrew Bollen, Margaret Wrensch, J. Gregory Cairncross, Burt G. Feuerstein
  [show abstract] [hide abstract]
  ABSTRACT: Gliomas that aggregate in otherwise unremarkable families may have a heritable genetic basis. To determine the spectrum of genetic alterations in glioma-susceptible families, we examined tumor DNA from familial cases for regions of chromosomal gain or loss using comparative genomic hybridization (CGH). We compared chromosomal alterations within and among glioma families to those found in sporadic gliomas. A specific chromosomal abnormality common to the tumors of multiple unrelated probands with glioma or a specific chromosomal abnormality common to multiple affected persons in a single glioma-prone family would support the hypothesis of an inherited predisposition to glioma and at the same time identify specific regions of the genome harboring putative glioma susceptibility genes. Tumor DNA from 11 patients from seven families with two or more individuals with glioma was analyzed, including three members of a remarkable family having 10 affected individuals. We found no chromosomal abnormality common to all tumors of all probands nor did we find family-specific abnormalities in two of three glioma-prone kindreds. There were frequent copy number aberrations (CNAs) on chromosomes 7, 10, 19, and the sex chromosomes; other CNAs included +3q(13.3-29), −4q, +5q, −9q34, +12, −13q(21 → 33), −15, −16p, +17qter, −18, −21, and −22. Amplifications occurred at ++7p(11.1 → 12), ++7q(21.2 → 33), ++12q(13.2 → 14), and ++12p(11 → 12). Although there were several novel CNAs [−16p, and ++12p(11-p12)], none could readily explain the inheritance of these tumors.
  Cancer Genetics and Cytogenetics.