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Cytogenetic study of acoustic neuroma
LETTER TO THE EDITOR Cytogenetic Study of Acoustic Neuroma
Acoustic neuromas are tumors that derive from Schwann cells surrounding the vestibular branch of the eighth cranial nerve. Bilateral acoustic neuroma is the hallmark of central neurofibromatosis, an autosomal dominant disease, whereas acoustic neuromas also occur singly, as sporadic tumors. While recent molecular genetic studies of acoustic neuromas have suggested a link between these tumors and loss of information on chromosome 22 [1, 2] in both central neurofibromatosis and sporadic tumors, there have been few cytogenetic studies of acoustic neuromas. We report the results of chromosome analysis of 11 acoustic neuromas. All analyses were from ceils grown in primary culture using previously described methods [3]. The tumors were grown in culture for 7-20 days; a minimum of 20 G-banded metaphases were analyzed from each specimen. Three specimens did not grow adequately for analysis; the remaining eight specimens were all diploid, with normal stemline karyotypes, except for one tumor from a 69-year-old man, in which the karyotype was 46,XY/45,XY,- 22/44,X,-Y,-22. Monosomies of selected chromosomes were observed in fewer than three cells per specimen in several tumors, including monosomy of chromosome 22 (two tumors), monosomy of chromosome 21 (three tumors), and monosomy of chromosome 4 (two tumors). Only rare cells had structural abnormalities or chromosome trisomies. These results are similar to the few existing reports of neuromas in the literature. Rey et al. studied seven neuromas (three acoustic and four spinal) and found normal diploid stem line karyotypes, with monosomy 22 in sideline karyotypes of three tumors [4]. Monosomies of chromosomes 18 and 22, inv(9), and 5q+ were observed in minorities of cells from the three acoustic tumors studied by Rogatto and Casartelli [5]; in contrast, they found monosomy 22, a dicentric chromosome involving chromosomes 6 and X, and a pericentric chromosome 9 in a spinal neurinoma. An acoustic neuroma from a patient with central neurofibromatosis was cytogenetically normal
[6]. Our results can be interpreted in several ways. First, because sufficient numbers of mitotic cells were obtained for study only after at least I week in culture, overgrowth of karyotypically abnormal tumor cells by normal cells may have occurred, resulting in the finding of predominantly normal karyotypes. Alternatively, acoustic neuromas may have karyotypes that deviate little from the normal at the light microscope level. Combined molecular and cytogenetic studies will help to elucidate the genomic characterization of these tumors. Supported by CA46289-03 from the National Cancer Institute. HEATHER D. WEBB
CONSTANCE A. GRIFFIN
The Johns Hopkins Oncology Center Cytogenetics Laboratory, Room 1-109 600 N. Wolfe St. Baltimore, MD 21205
83 © 1991 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, N e w York, NY 10010
Cancer Genet Cytogenet 5 6 : 8 3 - 8 4 (1991) 0165-4608/91/$03.50
84
H . D . Webb and C. A. Griffin
REFERENCES 1. Seizinger BR, Martuza RL, Gusella JF (1986): Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuromas. Nature 322:644-647. 2. Seizinger BR, Rouleau G, Ozelius LJ, Lane AH, St. George-Hyslop P, Huson S, Gusella iF, Martuzza RL (1987): Common pathogenic mechanism for three tumor types in bilateral acoustic neurofibromatosis. Science 236:317-319. 3. Griffin CA, Hawkins AL, Packer RJ, Rorke LB, Emanuel BS (1988): Chromosome abnormalities in pediatric brain tumors. Cancer Res 48:175-180. 4. Rey JA, Bello MJ, DeCampos JM, Kusak ME, Moreno S (1987): Cytogenetic analysis in human neurinomas. Cancer Genet Cytogenet 28:187-188. 5. Rogatto SR, Casartelli C (1989): Cytogenetic study of human neurinomas. Cancer Cenet Cytogenet 41:278, B19. 6. Wullich B, Kiechle-Schwarz M, Mayfrank L, Schempp W (1989): Cytogenetic and in situ DNA-hybridization studies in intracranial tumors of a patient with central neurofibromatosis. Hum Genet 82:31-34.
Acoustic neuromas are tumors that derive from Schwann cells surrounding the vestibular branch of the eighth cranial nerve. Bilateral acoustic neuroma is the hallmark of central neurofibromatosis, an autosomal dominant disease, whereas acoustic neuromas also occur singly, as sporadic tumors. While recent molecular genetic studies of acoustic neuromas have suggested a link between these tumors and loss of information on chromosome 22 [1, 2] in both central neurofibromatosis and sporadic tumors, there have been few cytogenetic studies of acoustic neuromas. We report the results of chromosome analysis of 11 acoustic neuromas. All analyses were from ceils grown in primary culture using previously described methods [3]. The tumors were grown in culture for 7-20 days; a minimum of 20 G-banded metaphases were analyzed from each specimen. Three specimens did not grow adequately for analysis; the remaining eight specimens were all diploid, with normal stemline karyotypes, except for one tumor from a 69-year-old man, in which the karyotype was 46,XY/45,XY,- 22/44,X,-Y,-22. Monosomies of selected chromosomes were observed in fewer than three cells per specimen in several tumors, including monosomy of chromosome 22 (two tumors), monosomy of chromosome 21 (three tumors), and monosomy of chromosome 4 (two tumors). Only rare cells had structural abnormalities or chromosome trisomies. These results are similar to the few existing reports of neuromas in the literature. Rey et al. studied seven neuromas (three acoustic and four spinal) and found normal diploid stem line karyotypes, with monosomy 22 in sideline karyotypes of three tumors [4]. Monosomies of chromosomes 18 and 22, inv(9), and 5q+ were observed in minorities of cells from the three acoustic tumors studied by Rogatto and Casartelli [5]; in contrast, they found monosomy 22, a dicentric chromosome involving chromosomes 6 and X, and a pericentric chromosome 9 in a spinal neurinoma. An acoustic neuroma from a patient with central neurofibromatosis was cytogenetically normal
[6]. Our results can be interpreted in several ways. First, because sufficient numbers of mitotic cells were obtained for study only after at least I week in culture, overgrowth of karyotypically abnormal tumor cells by normal cells may have occurred, resulting in the finding of predominantly normal karyotypes. Alternatively, acoustic neuromas may have karyotypes that deviate little from the normal at the light microscope level. Combined molecular and cytogenetic studies will help to elucidate the genomic characterization of these tumors. Supported by CA46289-03 from the National Cancer Institute. HEATHER D. WEBB
CONSTANCE A. GRIFFIN
The Johns Hopkins Oncology Center Cytogenetics Laboratory, Room 1-109 600 N. Wolfe St. Baltimore, MD 21205
83 © 1991 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, N e w York, NY 10010
Cancer Genet Cytogenet 5 6 : 8 3 - 8 4 (1991) 0165-4608/91/$03.50
84
H . D . Webb and C. A. Griffin
REFERENCES 1. Seizinger BR, Martuza RL, Gusella JF (1986): Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuromas. Nature 322:644-647. 2. Seizinger BR, Rouleau G, Ozelius LJ, Lane AH, St. George-Hyslop P, Huson S, Gusella iF, Martuzza RL (1987): Common pathogenic mechanism for three tumor types in bilateral acoustic neurofibromatosis. Science 236:317-319. 3. Griffin CA, Hawkins AL, Packer RJ, Rorke LB, Emanuel BS (1988): Chromosome abnormalities in pediatric brain tumors. Cancer Res 48:175-180. 4. Rey JA, Bello MJ, DeCampos JM, Kusak ME, Moreno S (1987): Cytogenetic analysis in human neurinomas. Cancer Genet Cytogenet 28:187-188. 5. Rogatto SR, Casartelli C (1989): Cytogenetic study of human neurinomas. Cancer Cenet Cytogenet 41:278, B19. 6. Wullich B, Kiechle-Schwarz M, Mayfrank L, Schempp W (1989): Cytogenetic and in situ DNA-hybridization studies in intracranial tumors of a patient with central neurofibromatosis. Hum Genet 82:31-34.