(CANCER RESEARCH 51, 1684-1688. March 15. 19911
Chromosome 9 Deletion Mapping Reveals Interferon a and Interferon ß-1
Gene
Deletions in Human Glial Tumors
C. David James,1 Ju He, Elisabeth Carlbom, Magnus Nordenskjold, Webster K. Cavenee, and V. Peter Collins
Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202 [C. D. J., J. H.]; Departments of Neurosurgery [E. C.] and Clinical Genetics [M. N.J,
Kamlinska Hospital, Stockholm, Sweden; Ludwig Institute for Cancer Research, Montreal, Canada ¡W.K. C.]; and Ludwig Institute for Cancer Research, Stockholm,
Sweden H. P. C.]
ABSTRACT
We have applied restriction fragment length polymorphism analysis
to a 30-member panel of primary glioma DNAs, which had been previ
ously examined for loss of genetic information (C. D. James, E. Carlbom,
J. P. Dumanski, M. Hansen, M. Nordenskjold, V. P. Collins, and W. K.
Cavenee, Cancer Res., 48:5546-5551, 1988), to determine the frequency
and sublocalization of loss of genetic information from chromosome 9.
We have also utilized scanning densitometry for dosage determination of
the 9p-localized Interferon a and Interferon ß-\genes among these same
tumors. Our results reveal the following: (a) for those cases in which
loss has occurred, the region of common loss lies on the short (p) arm of
the chromosome; (/»)
loss of genetic information from the short arm of
chromosome 9 occurs frequently in glial tumors of intermediate (anaplastic, grade III) and high (glioblastoma, grade IV) histológica!malig
nancy (10 of 20 cases) but not in tumors of low (grade II) histológica!
malignancy (0 of 10 cases); (c) tumors with 9p deletions are hemi- or
nullizygous for interferon ,J-1 and the Interferon a gene cluster; (d) cases
of interferon nullizygosity occur exclusively among tumors of highest
histológica!malignancy (glioblastoma). These data, especially the deter
mination of a region of nullizygosity, suggest proximity to or residence
within a gene(s) whose function!s) is (are) critical to the suppression of
the malignant evolution of glial tumors.
INTRODUCTION
RFLP2 analysis has been used extensively to examine tumor
DNAs for the purpose of localizing and identifying genes whose
products suppress tumor initiation (1,2) and/or progression
(3, 4). We have previously applied this method of analysis to
the most common form of primary central nervous system
tumor, the gliomas, to determine the genomic locations of
frequent loss of genetic information among such tumors (5, 6).
The results from these studies indicated that loss of genetic
information from the region 17pl 1.2-pter was the only genetic
alteration observed among members of each malignancy grade
of glioma and that loss from chromosome 10 occurred fre
quently and exclusively in the most malignant of gliomas, the
glioblastomas. These data therefore could be interpreted as
indicating that genetic alterations accumulate in glial tumors
during their malignant evolution (3).
In our initial study (5), a single marker near the centromere
on the long arm of chromosome 9 (7, 8) was used to examine
gliomas for loss of genetic information from this chromosome.
Since 9p deletions are a frequently cited structural alteration in
gliomas (9-11), and because of the recent determination of 9plocalized IFN nullizygosity in cell lines derived from malignant
gliomas (12), we have undertaken a more detailed RFLP analy
sis of chromosome 9 in primary glial tumors. A deletion-
mapping approach (6, 13) was used, and results were obtained
which suggest that the short arm of chromosome 9 harbors a
tumor suppressor gene (or genes) whose loss(es) is (are) fre
quently involved in the evolution of these tumors. The deter
mination of 9p-localized IFN nullizygosity in six highly malig
nant gliomas (glioblastomas) provides additional evidence in
support of this interpretation.
MATERIALS
AND METHODS
Human Tissue Samples. Human glioma samples were obtained from
34 patients between 11 and 74 years of age. Tumor diagnoses were
made according to the World Health Organization criteria (14) and the
criteria of Burger et al. (15) when distinguishing AA from GB. Thirtytwo of the tumors were from adult patients (>18 years of age); tumors
GB9 and A5 (Fig. 10) were from pediatrie patients. Two tumors (AA3
and AA4) were obtained by surgical resection of tumor regrowth in
patients who had undergone radiation and/or chemotherapy treatment
following initial surgical resection of the primary tumor; all other
specimens were obtained from initial surgeries from patients who had
not received any treatment. Fresh tumor specimens were frozen 0-3
years before isolation of DNA: peripheral venous blood was obtained
from 30 of the patients (Fig. IB) before surgery as a source of normal
control DNA for the RFLP analysis; no control DNA was available for
GB patients 13-16 (Fig. 3).
DNA Extraction, Southern Blotting, and Probe Hybridization. Cor
responding normal and tumor DNAs analyzed in this study had been
isolated as described previously (5). All tumor DNAs examined in this
study were prepared from macroscopically pure tumor tissue from
which a small sample was taken for histopathological analysis and
confirmation of high tumor cell content. DNA samples were digested
to completion with restriction enzymes (Boehringer Mannheim or
Pharmacia), electrophoresed, transferred to a nylon membrane (Nytran;
Schleicher and Schuell), and hybridized to probes radiolabeled by nick
translation (16) or random oligonucleotide-priming (17) procedures.
The chromosome 9 loci examined (Fig. \A) and their corresponding
DNA probes included: IFNBÌ
(pSY2051), IFNA (a-IFN),AS.S'(ASSg3),
D9S1 (pHF12-8), D9S7 (pEFD126.3), D9S10 (pMCT1326), and
D9S16 (pMCOA12). Information about probes pSY2051 and ASSg3
was obtained from their distribution source, American Type Culture
Collection; information concerning all other probes can be obtained in
Human Gene Mapping 10(18).
Scanning Densitometry. To determine allelic and/or gene dosages,
autoradiograms resulting from exposure to filters hybridized with the
IFNBÌand/or ¡FNAprobes were examined by scanning densitometry
with an LKB Ultroscan XL, and peak areas corresponding to each
hybridization signal were calculated by electronic integration. Follow
ing their exposure to film, filters were stripped of probe in 0.4 M NaOH
at room temperature for 15 to 30 min and recycled many times by
Received10/29/90;accepted1/8/91.
The costs of publication of this article were defrayed in part by the payment
successive hybridizations with syntenic and/or nonsyntenic probes. The
of page charges. This article must therefore be hereby marked advertisement in
control
probes used for dosage determination were chosen by revealing
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1Current address: Department of Pediatrics. Emory University SOM. 2040
maintenance of constitutional heterozygosity in the tumor DNA. IFNA
Ridgcwood Drive N.E.. Atlanta. GA 30322.
and IFNBI hybridization signals were normalized against the signal
2The abbreviations used are: RFLP, restriction fragment length polymor
produced by control probes to derive their dosage values in the tumor
phism: IFN, interferon: AA. anaplastic astrocytoma: GB. glioblastoma: A. astrosamples.
cytoma: cDNA. complementary DNA; LOH. loss of hcterozygosity.
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INTERFERON
GENE DELETIONS IN GLIAL TUMORS
RESULTS
A 30-member panel of normal-glioma DNA pairs was ex
amined with seven chromosome 9 markers. Of the probes used,
five have been localized to the long (q) arm of the chromosome
(Fig. IA). The two remaining markers, cDNA probes for the
1FNA and IFNB1 genes, reside on the short arm of the chro
mosome. Of these two 9p-localized probes, only the one for the
IFNB1 locus proved useful for analysis of LOH. As reported
by Ohlsson et al. (19), IFNBl probes reveal alleile restriction
fragment variants for Banll and Msp\ digests; the Banll poly-
OB
Grade IV
OB
1*
I«
Grade III
Grade II
2«
2«
2«
2
Fig. 1. Loss of genetic information from chromosome 9 in adult gliomas. A,
linear chromosomal order of loci investigated in this study using RFLP analysis
(7, 8). B, chromosome 9 loci zygosity in gliomas. Normal-tumor DNA pairs were
analyzed for loss of heterozygosity at the loci indicated. 2, tumor DNA mainte
nance of heterozygosity; /, loss of heterozygosity (locus hemizygosity); 0, tumor
DNA nullizygosity. In those cases in which no entry has been made for q-arm
loci, the patient's constitutional DNA was either uninformative or not tested.
Tumor designations: GB, glioblastoma; AA, anaplastic astrocytoma; AO, anaplastic oligodendroglioma; AOA, anaplastic oligoastrocytoma; A, astrocytoma: O,
oligodendroglioma; OA, oligoastrocytoma. ', patients whose IFNBl dosage was
determined by scanning densitometry only. The dosage values for these patients
were: GB3, 0.15; GB4, 0.19; GB10. 1.88; GB11. 2.15; GB12. 2.06; AA2. 0.90;
AA3, 1.15; AA5, 2.11; AA6, 2.03; A3, 2.12; A4, 2.07; AS, 2.11; Ol. 1.91; O2.
2.08; and O3, 1.96. The formula used to calculate these values is:
IFNBl,
HL,
IFNBl,
HL,
-x 2
where IFNBl represents the signal response for the interferon rfl probe pSY2051
in corresponding normal (n) and tumor (f) DNA samples and HL represents the
signal response at a locus in which the tumor DNA displayed maintenance of
heterozygosity. Using this formula, a value of 2.00 would represent a normalized
tumor DNA IFNBl signal response equivalent to that produced by the correspond
ing, normalized control DNA.
morphism is also revealed by Sad digests.
Fifteen of the patients were constitutionally heterozygous for
one or both of the /F/Vfi/-restriction enzyme combinations, and
six of these (GB1, GB2, GB5, GB6, AA1, and AO1; see Fig. 1
for explanation of abbreviations used for tumor classification)
revealed loss of one or both alÃ-elesin their corresponding tumor
DNA (Fig. IB). Of these six patients, one (GB2) revealed LOH
at a single informative (constitutionally heterozygous) q-arm
locus; the five remaining patients displayed maintenance of
heterozygosity at all informative q-arm loci (e.g., GB6 and AA1
in Fig. 2).
Scanning densitometry was used to evaluate IFNBl signal
response in all tumor DNAs to determine IFNBl gene dosage
in these tumors. Such analysis revealed that all reductions to
homozygosity (or LOH) and nullizygosity were associated with
one and zero IFNBl gene dose(s), respectively. In instances of
nullizygosity, the residual tumor DNA IFNBl signal (relative
response always <10% of normal) corresponded well with the
estimated normal cell content of the histopathological control
specimen ("Materials and Methods"). This type of analysis
further revealed that among the 15 patients who were uninformative (constitutionally homozygous) for IFNBl there were
two cases of tumor DNA IFNBl hemizygosity (AA2 and AA3)
and two additional cases of nullizygosity (GB3 and GB4). The
combined RFLP and gene dosage analysis revealed, therefore,
that 10 of the tumors examined in this series had lost one or
both IFNBl alÃ-eles(summarized in Fig. 1; see Fig. 2 for
examples). Six of these were malignancy grade IV (glioblas
toma) and four were malignancy grade III (anaplastic) tumors.
All tumor DNA IFNBl nullizygosities were observed among
the glioblastomas.
Twenty-eight of the 30 adult glioma patients were informative
at one or more of the q-arm loci examined; of these informative
cases, 3 displayed loss of heterozygosity from 9q (e.g., GB4 in
Fig. 2). Two of these patients were nullizygous (GB2, GB4) and
the third was hemizygous (AA2) at the IFNBl locus (Fig. 1).
The results of the densitometric analysis can also be used to
consider the chromosomal mechanisms (1) associated with
losses of genetic information from chromosome 9. Since zero
or one alÃ-elecopies were determined for each such loss (Fig. 1),
mitotic recombination and chromosome reduplication can be
excluded as associated mechanisms. Therefore, cases displaying
/FAW-specific loss (GB1, GB3, GB5, AA1, AA3, and AO1)
occurred through simple p-arm-specific deletions (e.g., GB6
and AA1 in Fig. 2); case AA2, whose tumor DNA displayed a
single alÃ-eledose for both q- and p-arm markers, presumably
arose from chromosomal nondisjunction. Two of the tumors
which revealed IFNBl nullizygosity (GB2, GB4) displayed loss
of a single q-arm alÃ-ele,suggesting the occurrence of both
chromosomal nondisjunction and partial p-arm-specific loss.
To further investigate the deletion of chromosome 9 se
quences in glial tumors, the 9p-localized 1FNA loci were ana
lyzed by hybridizing several filters with a cDNA probe for
human IFN-«2 for the purpose of assessing relative tumor
DNA IFNA dosage. Unlike the single-copy IFNBl gene, IFNA
is encoded by a gene family in humans (20, 21). This family
consists of at least two subfamilies, each of which contain
functional IFNAs and nonfunctional pseudogenes. Both IFNA
subfamilies reside on the short arm of chromosome 9 in close
cytogenetic and linkage proximity to the IFNBl gene. In total,
the number of IFNA genes and pseudogenes in the human
genome may be as high as 30 and the signal response resulting
from hybridization of the IFN-«2 cDNA to filter-bound gen-
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INTERFERON GENE DELETIONS IN GLIAL TUMORS
»P
N T
N T
GB6
2.2
2.0
D9S10
Pst l
Fig. 2. Chromosome 9 deletion-mapping
dala revealing 9p as the region of common loss
in malignant gliomus. Normal (,V)-tumor (T)
DNA pairs were examined for loss of genetic
information with the locus-enzyme combina
tions indicated beneath each autoradiogram.
Lt'ft ordinate*, alÃ-eledesignations; right ordi
nales, alÃ-elesi/es in kilobases. All designations
are according to Human Gene Mapping 10
(18) except for the ASS-Pstl combination
which is described in Ref. 30. ÕÕB6
and AAI,
examples of malignancy grades IV and III
gliomas displaying //r.VÄ/-specific LOH
(IFNBI hemizygosity): GBI and (iB4. exam
ples of malignancy grade IV tumors displaying
IFNBI nullizygosity (each of these patients
displayed constitutional homozygosity of the
3.9-kilobase, C2 alÃ-ele).Msp\ results displayed
for patients GB1 and GB4 were obtained by
hybridization and rehybridization of the same
filter with probes from the loci indicated. C,
nonsyntenic control probe (locus) used for de
termination of relative amounts of normal and
tumor DNA on Msp\ filters. ", the 1.3- and
1.6-kilobase restriction fragments which con
stitute the A2 alÃ-eleof loeus D3S2 were not
resolved on this gel. b, our estimation of the
alÃ-elelengths for this locus-enzyme combina
tion were slightly different from those reported
previously (6.0 and 4.3 kilobases: Ref. 30).
D2
AA1
3.0
•2.6
D1
IFNBI
Ban N
N
A2
2.5
GB1
C2 •
3.»
2.9
A1
A2
T
•• 1.3,1.6
D3S2
A2
GB4
Al
A2
5.0
4.0
omic digests is due to the presence of many complementary
sequences within a normal cell (19). For some restriction en
zymes (e.g., EcoRl), the restriction fragment patterns resulting
from IFN-«2cDNA hybridization reveal a few constant bands
and no polymorphism, and we have used such patterns to
analyze IFNA dosage. Densitometric analysis of 1FNA signal
response among the 30-member panel of patient normal-tumor
DNA pairs revealed a tumor IFNA signal response which con
firmed IFNBI deletion in each case of deletion (e.g., GB1, GB2,
GB5, GB6, and AA3 in Fig. 3). In four additional glioblastomas
for which there was no normal control DNA (GBs 13-16),
IFNA nullizygosity was evident in 2 cases (GB 14 and GB 15).
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INTERFERON GENE DELETIONS IN GLIAL TUMORS
Table 1 Genetic alterations in gliomas with chromosome 9 deletions
-, losses of genetic information. Arm-specific loss has been indicated from
those chromosomes and cases in which such specificity was determined (6). Loci
and corresponding probes used to detect loss of genetic information on all
chromosomes other than 9 are listed in Refs. 5 and 6. For chromosome 9. IFNBI
(9p) hemi- and nullizygosity arc distinguished by the use of one or two, respec
tively, —9(p)entries. +. EGFR gene amplification.
All of the tumors examined in this study had been previously
subjected to extensive RFLP analysis and had been examined
for amplification of the EGFR and MYCN genes (5). Compar
ison of the data resulting from the deletion-mapping examina
tion of chromosome 9 with the data acquired previously reveals
that each of the tumor DNAs demonstrating 9p/IFN deletion
had suffered at least one additional alteration (Table 1).
alterations-9p.
TumorGBIGB2GB3GB4GB5GB6AA1AA2AA3AO1Genetic
+EGFR-9,
-9p. -10.
+EGFR-9p.
-9p. -10.
+EGFR-9.
-9p, -10. -11. -13, -17.
-22-9p.
-9p, -10,
+EGFR-9p.
-10.
+EGFR-9p.-17p-9.
-10. -22.
DISCUSSION
The data presented here, derived from restriction fragment
length polymorphism and gene dosage analysis, supports the
existence of a tumor suppressor gene(s) on the short arm of
chromosome 9 whose loss(es) is (are) a frequent event in the
development of malignant glioma. Since we were unable to
detect such loss in any tumors of low histological malignancy
(Fig. 1) and since such loss was only detected in tumors with
additional alterations (Table 1), these data suggest the 9p
deletions as an event of tumor progression (3, 4) rather than
initiation (1, 2).
In addition to this series of tumors occurring most commonly
in adults, 13 central nervous system tumors common to the
pediatrie age group have been examined for loss of genetic
information using the IFNB1 probe (22). Six of the 10 patients
with medulloblastoma and 2 of 3 patients with pilocytic astrocytoma were informative at this locus and none revealed loss of
genetic information. These data suggest, therefore, that 9p
deletions are specific to malignant central nervous system tu
mors which usually occur in adults.
The 30 tumors listed in Fig. 1 had been previously subjected
to RFLP analysis and, as can be seen in Table 1, loss of genetic
information among the tumors showing chromosome 9 and/or
9p deletions had been determined at several other genomic
locations. However, most of the LOH studies involving primary
human tumors, including our own, have only been successful
in determining the locations at which one of two alÃ-elesis lost.
The determination of a region which is entirely deleted or
altered in tumor tissue has previously indicated proximity to or
residence within a gene whose function is critical to the suppres
sion of tumor initiation and/or progression (23-26).
-17p-9p.
+EGFR-1.
-4, -9p. -21
Miyakoshi et al. (12) have recently reported that the IFN
genes on the short arm of chromosome 9 are frequently deleted
in cell lines established from malignant gliomas. In our initial
RFLP analysis of primary glial tumors, the sole marker used
from this chromosome had, through use of somatic cell hybrids,
been localized between 9ql 1 and 9pter (27); no loss of heterozygosity was observed with this marker. More recently, the
location of the sequence detected by this probe has been deter
mined to lie near the centromere on 9q (7, 8). As a result of
this new information, we initiated a study to examine the
incidence of 9p deletions in primary glial tumors. Our results
are entirely consistent with those described for cell lines derived
from the malignant gliomas (12) and indicate that such loss is
of significance in their in vivo clonal evolution (3). At this time,
the minimum region of deletion on 9p is not well defined.
However, in two of the glioblastomas analyzed in this study,
our dosage analysis indicated the presence of IFNBI DNA and
the nearly complete absence of IFN A DNA (GB 14, GB 15: Fig.
3). Therefore, the minimum common region of deletion which
is indicated at this time is that part of the short arm spanned
by the IFNA genes. The possibility that the IFN genes them
selves may function as tumor suppressor genes in glial cells,
and would therefore represent the target of 9p deletions, has
co
IO (O
CÛOÙOÙGÛÛÛ
GÛCD CD <C OÙQÛ
o o o o oooo<ooo
IFNA
DXYSI
<**>
IFNB1
Fig. Ì.
Comparison of relative IFNA and IFNBI dosage in malignant gliomas. £coRl-digested normal control (A7)and tumor ( T) DNAs were electrophoresed and
blot transferred to a nylon-based membrane. The filter was hybridized and rehybridized with the following probes: a-IFN (IFNA), pSY2501 (IFNBI), and pDP34
(DXYSI). The band displayed for IF\A corresponds to a 4.5-kilobase froRI restriction fragment described previously (31) and produces the most rapid signal
response among a few bands revealed by hybridization of the IFN-«2cDNA probe a-IFN to fcoRI-digested DNA (see "Results"). The intensity of all other IFNAcomaining restriction fragments revealed by this probe were reduced proportionately in tumor DNAs revealing a reduction in intensity of the band displayed. The
bands revealed by the IFNBI and DXYSI probes were the only bands revealed in EcoR I-digested DNA. DXYSI was selected as a signal standard since this probe
failed to reveal loss of heterozygosity (Taql digest; data not shown) in any of the tumor DNAs from 26 informative glioma patients among the 30 patients listed in
Fig. 1. Approximate restriction fragment sizes: DXYSI. 2 kilobases: IFNBI. 1 kilobases.
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INTERFERON
GENE DELETIONS IN GLIAL TUMORS
recently been considered in some detail ( 12). As a result of their
deletion, as determined by molecular and/or cytogenetic analy
sis, the 9p-localized IFNs have also been implicated as tumor
suppressor genes in leukemias (28) and malignant melanoma
(29). We believe that a conservative interpretation of the results
from these studies would call for the identification and devel
opment of markers from 9p which could be used to characterize
and define the region of deletion. However, the frequency of
IFN nullizygosity observed within this group of tumors lends
further support to their having a tumor suppressor gene role.
ACKNOWLEDGMENTS
We would like to thank Drs. M. Ohlsson, R. White, Y. Nakamura,
H. Northrup, W. O'Brien, and the American Type Culture Collection
for the probes used in this study.
REFERENCES
1. Cavenee, W. K., Dryja, T. P., Phillips, R. A., Benedict. W. F., Godbout, R.,
Gallic, B. L., Murphree, A. L., Strong, L. C., and White, R. L. Expression
of recessive alÃ-elesby chromosomal mechanisms in retinoblastoma. Nature
(Lond.), J05: 779-784, 1983.
2. Hansen, M. F., and Cavenee, W. K. Genetics of cancer predisposition. Cancer
Res.. 47:5518-5527. 1987.
3. Nowell, P. C. The clonal evolution of tumor cell populations. Science
(Washington DC), 194: 23-28, 1976.
4. Vogelstein, B., Fearon, E. R., Baker. S. J„Nigro. J. M.. Kern, S. E..
Hamilton, S. R., Bös,J., Leppert, M., Nakamura, Y., and White, R. Genetic
alterations accumulate during colorectal tumorigenesis. In: W. K. Cavenee,
N. Hastie, and E. Stanbridge (eds.), Recessive Oncogenes and Tumor
Suppression, pp. 73-80. Cold Spring Harbor, NY: Cold Spring Harbor
Laboratory Press, 1989.
5. James. C. D., Carlbom, E., Dumanski. J. P.. Hansen, M., Nordenskjold, M.,
Collins, V. P., and Cavenee, W. K. Clonal genomic alterations in glioma
malignancy stages. Cancer Res., 48: 5546-5551. 1988.
6. James. C. D., Carlbom, E., Nordenskjold, M., Collins, V. P., and Cavenee,
W. K. Mitotic recombination of chromosome 17 in astrocytomas. Proc. Nati.
Acad. Sci. USA, 86, 2858-2862, 1989.
7. Lathrop. M., Nakamura. Y., O'Connell, P.. Leppert, M., Woodward, S..
Lalouel, J-M., and White, R. A mapped set of genetic markers for human
chromosome 9. Genomics, 3: 361-366, 1988.
8. Smith, M., and Simpson, N. E. Report of the committee on the genetic
constitution of chromosomes 9 and 10. Cytogenet. Cell Genet., 51: 202-225.
1989.
9. Jenkins, R. B., Kimmel, D. W.. Moertel. C. A., Schultz, C. G.. Scheithauer.
B. W., Kelly, P. J., and Dewald, G. W. A cytogenetic study of 53 human
gliomas. Cancer Genet. Cytogenet., 39: 253-279, 1989.
10. Bigner, S. H., Mark. J., Burger, R. C., Mahaley, M. S., Bullard. D. E.,
Muhlbaier, L. H., and Bigner. D. D. Specific chromosomal abnormalities in
malignant human gliomas. Cancer Res., 48: 405-411, 1988.
11. Rey, J. A., Bello, M. J., de Campos, J. M., Kusak, M. E., Ramos, C.. and
Benitez, J. Chromosomal patterns in human malignant astrocytomas. Cancer
Genet. Cytogenet., 29: 201-221, 1987.
12. Miyakoshi, J., Dobler, K. D.. Allalunis-Turner, J., McKean, J. D. S., Petruk,
K., Allen, P. B. R., Aronyk, K. N., Weir. B., Huyser-Wierenga, D., Fulton,
D., Urtasan, R. C, and Day, R. S. Absence of IFNA and IFNB genes from
human malignant glioma cell lines and lack of correlation with cellular
sensitivity to interférons.Cancer Res.. 50: 278-283, 1990.
13. Dumanski. J. P., Carlbom, E.. Collins. V. P., and Nordenskjold, M. Deletion
mapping of a locus on human chromosome 22 involved in the oncogenesis
of meningioma. Proc. Nati. Acad. Sci. USA, 84: 9275-9279, 1987.
14. Zulch, K. G. Histological Typing of Tumors of the Central Nervous System,
International Histological Classification of Tumors No. 21. Geneva, Swit
zerland: World Health Organization, 1979.
15. Burger, P. C., Vogel, F. S., Green, S. B., and Strike, T. A. Glioblastoma
multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic
implications. Cancer (Phila.). 56: 1106-1111. 1985.
16. Rigby, P. W.. Dieckmann, M.. Rhodes, C., and Berg. P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA
polymerase I. J. Mol. Biol.. 113: 237-251, 1977.
17. Feinberg, A. P., and Vogelstein, B. A technique for radiolabeling DNA
restriction fragments to high specific activity. Anal. Biochem., 132: 6-13,
1983.
18. Kidd, K. K., Bowcock, A. M., Schmidtke, J.. Track. R. K.. Ricciuti, F.,
Hutchings, F., Pale, A.. Pearson, P., and Willard, H. F. Report of the DNA
committee and catalogues of cloned and mapped genes and DNA polymor
phisms. Cytogenet. Cell Genet., 51: 622-947. 1989.
19. Ohlsson, M., Feder, J.. Cavalli-Sforza, L. L., and von Gabain, A. Close
linkage of alpha and beta interferons and infrequent duplication of beta
interferon in humans. Proc. Nati. Acad. Sci. USA, S2: 4473-4476, 1985.
20. Pestka, S., Langr, J. A., Zoon, K. C., and Samuel, C. E. Interferons and their
actions. Annu. Rev. Biochem., 56: 727-777, 1987.
21. Capon, D. J., Shepard, H. M., and Goeddel. D. V. Two distinct families of
human and bovine interferon alpha genes are coordinately expressed and
encode functional polypeptides. Mol. Cell. Biol., 5: 768-779, 1985.
22. James. C. D., He, J., Carlbom, E., Mikkelsen, T., Ridderheim, P-A., Cavenee,
W. K.. and Collins. V. P. Loss of genetic information in central nervous
system tumors common to children and young adults. Genes Chromosomes
Cancer, 2: 94-102. 1990.
23. Friend. S. H., Bernards, R.. Rogelj, S., Weinberg, R. A., Rapaport, J. M.,
Albert, D. M.. and Dryja, T. P. A human DNA segment with properties of
the gene that predisposes to retinoblastoma and osteosarcoma. Nature
(Lond.), 323: 643-646, 1986.
24. Baker. S. J., Fearon, E. R., Nigro. J. M., Hamilton, S. R., Precinger, A. C,
Jessup. J. M., vanTuinen, P., Ledbetter, D. H., Barker. D. F., Nakamura,
Y., and Vogelstein, B. Chromosome 17 deletions and p53 mutations in
colorectal cancer. Science (Washington DC), 244: 217-221, 1989.
25. Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E.. Simons, J. W., Ruppert,
J. M., Hamilton, S. R., Preisinger. A. C., Thomas, G., Kinzler, W., and
Vogelstein, B. Identification of a chromosome 18q gene that is frequently
altered in colorectal cancers. Science (Washington DC), 247:49-56. 1990.
26. Haber, D. A., Buckler, A. J.. Glaser. T., Call, K. M., Pelletier, J., Sohn, R.
L., Douglass, E. C., and Housman, D. E. An internal deletion within an
Ilpl3 zinc finger gene contributes to the development of Wilms' tumor.
Cell, 61: 1257-1269. 1990.
27. Naylor, S. L., Sakaguchi, A. Y., Barker, K., White, R., and Shows, T. B.
DNA polymorphic loci mapped to human chromosomes 3, 5, 9, 11, 17, 18,
and 22. Proc. Nati. Acad. Sci. USA, SI: 2447-2451, 1984.
28. Diaz, M. O., Aiemin, S.. Le-Beau. M. M.. Pitha. P., Smith, S. D., Chilcote,
R. R., and Rowley, J. D. Homozygous deletion of the alpha- and beta 1interferon genes in human leukemia and derived cell lines. Proc. Nati. Acad.
Sci. USA, 85: 5259-5263, 1988.
29. Cowan. J. M., Halaban, R., and Francke, U. Cytogenetic analysis of melanocytes from premalignant nevi and melanomas. J. Nati. Cancer Inst., 80:
1159-1164, 1988.
30. Northrup, H.. Lathrop, M., Lu, S. Y.. Daiger, S. P.. Beaudet, A. L., and
O'Brien, W. E. Multilocus linkage analysis with the human argininosuccinate
synthetase gene. Genomics, 5: 442-444, 1989.
31. Heneo, K.. Brosius, J., Fujisawa, A., Fujisawa. J. L, Haynes, J. R., Hochstadt,
J., Kovacic, T., Pasek, M., Schambock, A., Schmid, J., Todokoro, K.,
Walchli, M., Nagata, S., and Weissman, C. Structural relationship of human
interferon alpha genes and pseudogenes. J. Mol. Biol., 185: 227-260, 1985.
1688
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Chromosome 9 Deletion Mapping Reveals Interferon α and
Interferon β-1 Gene Deletions in Human Glial Tumors
C. David James, Ju He, Elisabeth Carlbom, et al.
Cancer Res 1991;51:1684-1688.
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