GENOMICS

13,‘i?%-300

(19%)

Chromosomal Localization in Man and Rat of the Genes Encoding the Liver-Enriched Transcription Factors C/EBP, DBP, and HNFl/ LFB-1 (CEBP, DBP, and Transcription Factor 1, TCFI, Respectively) and of the Hepatocyte Growth Factor/Scatter Factor Gene (HGF) CLAUDE SZPIRER,* MICHELE RIVIERE,* RICCARDO CofUEsE,t TOSHIKAZU NAKAMURA,$ G~RAN LEVAN, 5 AND JOSIANE SZPIRER* *D&partement tlnstituto

M. QUAMRUL

ISLAM,§

de Biologie Mol&ulaire, Universite’ Libre de Bruxelles, Rue des Chevaux, 67, B-l 640 Rhode-St-Get&e, Belgium; di Ricerche di Biologia Molecolare, Via Pontina Km. 30600, 1-00040 Pomezia, Italy; SDepartment of Biology, Faculty of Science, Kyushu University, Fukuoka 812, Japan; and §Department of Genetics, University of Gothenburg, Box 3303 7, S-40033 Gb’teborg, Sweden Received

October

4, 1991;

By means of somatic cell hybrids segregating either human or rat chromosomes, we determined the chromosome localization of three genes encoding transcription factors expressed in hepatocytes, namely, C/EBP (CCAAT/enhancer binding protein), DBP (D site of albumin promoter binding protein), and HNFl/LFB-1 (designated transcription factor 1, gene symbol: TCFl), and of the hepatocyte growth factor gene, which is identical to the mitogenic and chemotactic factor designated scatter factor (gene symbol: HGF). The CEBP and DBP genes, encoding two related transcription factors, were found to be syntenic both on human chromosome 19 and on rat chromosome 1. These results provide further evidence for conservation of synteny on these two chromosomes (and on mouse chromosome 7). The TcFl gene was found to be located on chromosome 12 in both man and rat, thereby defining a new segment of homology between these two species (and a segment of mouse chromosome 5). The HGF gene was mapped to rat chromosome 4, confirming homology between this chromosome and human chromosome 7, which carries the human HGF gene. 0 1992 Academic Press, Inc.

INTRODUCTION

Several DNA-binding proteins involved in the expression of genes preferentially expressed in hepatocytes have been identified and their genes cloned (for a recent review, see Johnson, 1990). These transcription factors are likely to play a pivotal role in the control of hepatocyte differentiation, and abnormal expression or structural alterations of the corresponding genes might be involved in the process of tumorigenesis. In this respect, factors affecting hepatocyte growth are obviously also important (for a recent review, see Michalopoulos, 1990). From the standpoint of both formal gene mapping and cancer genetics, it would thus be interesting to know the chromosome localization of genes encoding transcription and growth factors. 293

revised

February

5, 1992

Among the liver-enriched transcription factors are DNA-binding proteins that interact with similar sites, and in particular with the albumin promoter D site: C/ EBP (i.e., CCAAT box/enhancer binding protein; Landschultz et al., 1988), DBP (i.e., D site of albumin promoter binding protein; Mueller and Maire, 1990), and ILGDBP/LAP/NF-IL6 (interleukin-6-dependent DNA-binding protein/liver activating protein/nuclear factor-IL6; Poli et al., 1990; Descombes et al., 1990; Akira et al., 1990). The gene encoding ILGDBP/LAP/ NF-IL6 (designated TCF5) was assigned to chromosome 20 in man and to chromosome 3 in rat (Szpirer et al., 1991a). We have now extended this mapping work to the human and rat CEBP and DBP genes. HNFl (hepatic nuclear factor 1, also named LF-Bl) is a hepatic factor belonging to the POU domain protein family (Courtois et al., 1988; Frain et al., 1989; Baumhueter et al., 1990; Bach et al., 1990). The corresponding gene, designated TCFl (transcription factor l), has recently been mapped in both man (chromosome 12q24.3) and mouse (chromosome 5, band F) (Kuo et al, 1990; Bach et al., 1990). We independently assigned the TCFl gene to human chromosome 12 and also mapped it in the rat. A potent mitogen for hepatocytes is the hepatic growth factor (HGF), also known as hepatopoietin A (HPTA) (Nakamura et al., 1989; Michalopoulos, 1990; Tashiro et al., 1990); this protein is also identical to the motogenic and chemotactic factor termed scatter factor (Gherardi and Stoker, 1991; Weidner et al., 1991). We confirmed the recent assignment of the human HGF gene to chromosome 7 (Weidner et al., 1991; Fukuyama et al., 1991) and also mapped the rat HGF gene. MATERIALS

AND

METHODS

Two panels of somatic cell hybrids were used to localize the genes in man and rat: a panel of human X mouse or human X rat hybrids that oss43-7543/92 $5.00 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.

294

SZPIRER

17-

6.55-

FIG. 1. Localization of the human CEBP gene. Autoradiogram of a Southern blot of BamHI-digested DNAs: mouse (M: A9 cells, carrying the Cebp” allele), human (H), rat (R), and mouse X human hybrids (HA11 and HB181) or rat X human hybrids (JVOl and HR40C8). The sizes of the fragments are indicated in kilobases. segregate human chromosomes and a panel of rat X mouse hybrids that segregate rat chromosomes. Both panels were described previously and have been used to localize several human and rat genes, respectively (Wathelet et al., 1988, Wendel-Hansen et al., 1990; Islam et al., 1989; Szpirer et al., 1984, 1991a,b; Levan et al., 1990, 1991). The human X rodent cell hybrids were derived from the fusion of human fibroblasts with either mouse cells (A9 and B82, generating HA and HB hybrids, respectively) or rat cells (JFl and Rat2, generating JV and HR hybrids, respectively). The rat X mouse hybrids were derived from the fusion of mouse BWTG3 hepatoma cells with Sprague-Dawley rat hepatocytes (Szpirer et al., 1984). Chromosome preparations were made as described previously (Szpirer et al., 1984). Some more recent analyses were made with slight modifications to the fixation procedures (Islam and Levan, 1987) and led to a few modifications in the chromosome constitution of the hybrids used (see Tables 1 and 2); however, none of these minor changes affects our previous assignments. DNA was extracted and analyzed by the Southern blot method (Southern, 1975), after blotting to nylon membrane. The following probes were used: for the CEBP gene-a 0.9.kb HindIII-PuuII fragment from the 3’ region of the rat cDNA (plasmid pMSV-CEBP) (Friedman et al., 1989); for the DBP genes-a 1.6-kb EcoRI fragment corresponding to the full-length rat cDNA fragment (plasmid DBP-l88) (Mueller and Maire, 1990); for the TCFl genes (HNFl/NFB-1 factor)-a 2.4.kb EcoRI fragment from the rat cDNA X16 clone (plasmid BSB-B3kb) (Frain et al., 1989); for the human HGF gene-the 0.7.kb MluI-Sal1 insert from the human HGF cDNA (plasmid KK232-DEP5) (Nakamura et al., 1989); for the rat HGF gene-the 1.4-kb EcoRI insert from the rat cDNA (plasmid pRBC1) (Tashiro et al., 1990). The probes were labeled by the random priming method (Feinberg and Vogelstein, 1984).

ET

AL.

showed a BamHI restriction fragment of 5.0 kb, and the rat DNA a BamHI fragment of 6.5 kb (Figs. 1 and 2). The mouse DNA was of different origin in the human X mouse and rat X mouse hybrids and, as previously reported (Birkenmeier et al., 1989; Xanthopoulos et al., 1989), showed a BamHI restriction fragment polymorphism: the DNA from the A9 and B82 fibroblasts (of C3H origin and used to generate the human X mouse hybrids) yielded a BamHI restriction fragment of about 17 kb (Fig. 1; allele Cebp”; Birkenmeier et al., 1989), whereas the DNA from the BWTG3 cells (of C57L origin and used to generate the rat X mouse hybrids) showed a BamHI restriction fragment of 10 kb (Fig. 2; allele Cebpb). In the human X rodent hybrids, the human CEBP gene segregated with human chromosome 19 (results illustrated in Fig. 1 and summarized in Table 1). Several discordant clones were counted for each of the other chromosomes. The hybrid HA232 lacks intact human chromosome 19 but has been shown previously (Wendel-Hansen et al., 1990 and unpublished data) to contain genes located in the region 19q13.1-q13.3 (PSBGl, CEA, and LHB genes) (Niemann et al., 1989; &honk et al., 1989; Julier et al., 1984). Since this hybrid lacks the human CEBP gene, we conclude that the CEBP gene resides on chromosome 19, outside the segment q13.1q13.3. In the rat X mouse hybrids, the rat CEBP gene segregated with rat chromosome 1 (Fig. 2 and Table 2), and several discordant clones were counted for each of the other chromosomes. Assignment of the Human and Rat DBP Genes Sac1 was used to detect the human DBP gene in DNA from the human x rodent hybrids: as illustrated in Fig. 3, a human 6.6-kb fragment could be distinguished from T

0 M

R

F;

g

RESULTS

The human and rat genes were localized by Southern blot analysis of DNA isolated from human x rodent (mouse or rat) and from rat X mouse somatic cell hybrids, respectively. Assignment of the Human and Rat CEBP Genes As illustrated in Fig. 1 (human CEBP) and Fig. 2 (rat CEBP), BamHIII digestion allowed us to follow the human or rat CEBP gene in the hybrids. The human DNA

FIG. 2. Localization of the rat CEBP gene. Autoradiogram of a Southern blot of BamHI-digested DNA: mouse (M: BWTG3 cells, carrying the Cebp* allele), rat (R), and mouse X rat hybrids (LBBlO-I and LB251).

,”,,..,.”

-,,_

_.__l”_.-_.

of independent

+

discordant

+ + +

ND + + + -

+ -

-

TCFl

gene”

clones’

+ f + + +

-

+ + + -

-

-

HGF

6 6 5 8

+ + + (+I -

+ + + 3 3 4 6

1

X

5 5 5 4

+ f + + -

+

2

6 7

7 I

+ 7 I 6 9

8 8 7 7

+ -+ ~ + --~ ~+ + -

+ -+ + + i”, (=I + + ~ (-) -

+ + + (1, + + + + +

5

4

3

7

5 5 5 6

4 4 4 0=

6 6 4 I

++ -+ A A+ ++-

8

3 3 5 6

t-1

-

(+I + -

9

5 5 5 4

+ +

+

-

(+I +

10

Human

CEBP, DBP, TCFl,

+f - -(‘1 ++ +++- + + ++ - + +- ++

6

of the Human

1

+ -

+ + + + + + + + + + + -

11

,,

I

,,

4 4 4 3

7 I 5 6

+ +

+ + +

+ + (+) +

(+) + + + + +

14

~ (+) + -

13

3 3 5 5

+

+ + + + + + +

15

5 5 3 6

6 6 6 I

17

- -+- + (1, +- ++f +- +f -- ++ -- ++(I, ++

16

2 2 3 5

+ + + + + +

-

18

i 5

0=

+ +

C-Y + +

-

19

21

4 4 3 5

4 4 4 7

++ ++ -- + ++ +++ - +- ++ - +++ + -- -(1, +

20

22

Y

genes)

(see text).

the human chromosome is present in 25 to 55% of the metaphases; (-) chromosome is absent. identified by asterisks (HA11 and HA13; HA212 and HA232; HB25 and the hybrid in question was not taken into account to establish the number

4 4 =0 5

+ (+) + + + + + +

12

chromosome*

and HGF Genes

a A + or a - indicates the presence or absence of the human gene, respectively. b A + indicates that the human chromosome is present in more than 55% of the metaphases; (+) indicates that indicates that the human chromosome is present in less than 25% of the metaphases; - indicates that the human ’ Independent hybrid clones are clones derived from distinct fusion events. Pairs of nonindependent clones are HB29; HBlll and HB115). When a chromosome was present in less than 25 % of the metaphases (- in parentheses), of discordancies for that particular chromosome. ’ HA232 lacks intact human chromosome 19 but contains genetic material derived from 19q (CEA, PSGBI, LHB

Number CEBP DBP TCFI HGF

+

+ + -

-

+

HAll* HA13* HA212* HA232* HB25* HB29* HB34 HB43 HBlll* HB115* HB142-2 HB181 JVOl JVO61 JV211 HR40C8

+ + +

DBP

CEBP

Hybrid

Human

Assignment

TABLE

+ + +

+ + +

+

of independent

clones’

ND ND

ND ND

discordant

ND

-

+

+ + + + -

-

ND + + + + -

ND + + + + + + + ND + ND ND ND

9 9 6 5

+ +

+ + + + + + + ~ -

+

+ + + + + +

+ + +

f + + + +

X

HGF

TCFI

8 9

0= 0=

+

-

-

A-

2 + -

1

6 7

8 8

(+I + + + + + + + + + + +

2

-

8 6 4

9

+ f

+

(+I + + -

3

9 8 5 0

+ + + + + + + + + + + + + + + + +

4

of the Rat

5 4 9 8

+ + (+) + (-) -

5

5 5 7 6

+ + + + + +

(+I + -

7 6 3 4

(-) C-1 + +

+ +

+ + + + +

+ + +

+ (+) + -

7

6

5 5 11 11

+ +

+ -

-

8

CEBP, DBP, TCFl,

2

4 4 6 7

+

-

+ -

(-1 +

7 7 8 7

(+) +

+ + + -

+

7 7 8 6

+ + + + + + + + + + +

+~ -

(6) + + + -

+ +

-

11

10

chromosome*

9

Rat

and HGF Genes

5 5 0 z

+ + (+) + +

(=I (-) + + + + + + -

12

5 5 8 7

~++ +-+ (1, -+ --f

++ ++ ++ ++ ++ ++ ++f 8 8 6 4

14

13

7 7 6 5

+ + + + + + + + + +

-

~ +

15

9 9 6 5

+ + + + + + +

+ + + -

-

+

(I, + +

16

10 9 6 6

+ + + + + +

+ +

(+) (+) + -

17

8 8 7 6

+ + + + +

+ + + + +

-

+

+ + + +

18

4 4 5 7

+ + + + +

+ -

+ (+I + -

19

6 5 8 7

(-1 + (+) (+) +

-

(+) -

20

n A + or a - indicates the presence or absence of the rat gene, respective15 . __,.. ^ . (-) indicates that b A + indicates that the rat chromosome is present m more than 5Syi 01 the metaphases; (+) indicates that the rat chromosome is present in 25 to 55, % of the metaphases; the rat chromosome is present in less than 25% of the metaphases; - indicates that the rat chromosome is absent. c Independent hybrid clones are clones derived from distinct fusion events. They are identified by distinct numbers (nonindependent clones are labeled by asterisks: LBBlO-B and LBSlO-I; (- in parent.heses), the hybrid in question was not LB330 and LB330TG3; LB780 and LB780-6; the three LB1040 clones). When a chromsome was present in less than 25 % of the metaphases taken into account to establish the number of discordancies for that particular chromosome.

Number CEBP DBP TCFl HGF

ND -

ND

ND -

ND -

-

ND

LB20 LB150-1 LB161 LB210-B* LB210-I* LB251 LB330* LB330TG3’ LB510-6 LB600 LB630 LB780* LB780-6* LB810 LB860 LB1040TGl* LB1040TG3* LB1040TG5* BS511 BS14Ohl

DBP

CEBP

Hybrid

Rat gene”

Assignment

TABLE

E ‘d s !z 3 F

CHROMOSOMAL

LOCALIZATION

OF

CEBP,

DBP,

TCFI,

HGF

297

5.4-

3.5-

1.9 1.6 2.21.9 1.6-

FIG. 3. Localization of the human Southern blot of SacI-digested DNAs

DBP gene. Autoradiogram of a (same samples as in Fig. 1).

the mouse fragments (7.7 and 2.2 kb) and from the rat fragments (7.4, 2.2, 1.9, and 1.6 kb). Table 1 shows that the human DBP gene segregated with chromosome 19, as did the CEBP gene. These two genes are thus syntenic on chromosome 19. PstI generated restriction fragments at 5.4 and 1.6 kb in the mouse DNA and at 3.5 and 1.9 kb in the rat DNA. Southern analysis of the rat X mouse hybrid DNA (Fig. 4, Table 2) showed that the rat DBP gene segregated with rat chromosome 1, as did the CEBP gene. The two rat genes are thus also syntenic in the rat, on chromosome 1. Assignment of the Human and Rat TCFl Genes (HNFl/NFB-1 Factor) Hind111 was used to map the TCFl gene in the two species (Figs. 5 and 6). Restriction fragments were detected at 14 kb in human DNA (which also showed a faint band at 8.0 kb), at 17.0 kb in rat DNA, and at 8.0, 3.0, and 2.5 kb in mouse DNA. In each of the two hybrid panels, the TCFl gene segregated clearly with chromosome 12: the human gene with human chromosome 12 in the human X rodent hybrids (Fig. 5 and Table 1) and the rat gene with rat chromosome 12 in the rat X mouse hybrids (Fig. 6 and Table 2). In both cases, several discordant clones were counted for each of the other chromosomes. We can thus conclude that the TCFl gene resides on human and rat chromosomes 12. Assignment of the HGF Gene Using PstI, we showed that the human gene segregates with human chromosome 7 (Table l), in agreement with recent results (Weidner et al., 1991; Fukuyama et al., 1991).

FIG. 4. Localization of the rat DBP gene. Autoradiogram of a Southern blot of PstI-digested DNAs (same samples as in Fig. 2).

BamHI generated two rat restriction fragments at 8.4 and 7.2 kb and two mouse restriction fragments at 19.0 and 13.0 kb (Fig. 7). The rat gene unambiguously segregated in the rat X mouse hybrids with rat chromosome 4 (Table 2). DISCUSSION This study shows that two genes of the CEBP family, CEBP itself and DBP, are syntenic in man, on chromo-

1714-

FIG. 5. Localization of the human TCFl gene. Autoradiogram of a Southern blot of Hi&III-digested DNAs: mouse (M), human (H), rat (R), and mouse X human hybrids (HAll, HA13, HB181) or rat x human hybrids (JVO61 and HR40C8).

298

SZPIRER

M

R

;;+I-

8-

32.5-

FIG. 6. Localization of the rat TCFI gene. Autoradiogram of a Southern blot of Hi&III-digested DNAs: mouse (M), rat (R), and mouse X rat hybrids (LB210.I, LB780-6, and LB1040).

some 19, and in rat, on chromosome 1. Interestingly, another gene of the CEBP family, designated TCF.5, encoding the ILGDBP/LAP/NF-IL6 factor is not syntenic with CEBP and DBP: TCF5 resides on human chromosome 20 and on rat chromosome 3 (Poli et al., 1990; Descombes et al., 1990; Akira et al., 1990; Szpirer et al., 1991a). A synteny group containing at least three genes (GPI, PEPD, and CYP2Bl) is already known to be retained on rat chromosome 1 and human chromosome 19 (region 19q12-q13.2) (Yoshida, 1984; Rampersaud and Walz, 1987; Lusis et al., 1986; Miles et al., 1988; Levan et al., 1991). Our results thus add two related genes, CEBP and DBP, to this conserved synteny group. The mouse homologs of GPI, PEPD, CYP2B1, and CEBP have also been localized: they map on mouse chromosome 7, in the proximal region (Simmons and Kasper, 1983; Birkenmeier et al., 1989; Xanthopoulos et al., 1989; Nadeau and Reiner, 1989; Miles et al., 1990; Saunders and Seldin, 1990). The mouse Dbp gene might also reside on chromosome 7. With regard to the human genes, our data indicate that the CEBP and DBP genes (absent in the hybrid clone HA232) are localized outside the region (19q13.1-q13.3) containing the PSBl, CEA, and LHB genes (present in the hybrid clone HA232). Several genes defining the above-mentioned conserved synteny group (GPI, PEPD, and CYP2Bl) are located in the region 19q12-q13.2 (which also contains the hyperthermia susceptibility locus; McCarthy et al., 1990). It thus appears that if the conserved synteny group is not split, all its members, including CEBP and DBP, probably map in the 19q12-q13.1 region, more proximally than the PSBGl, CEA, and LHB genes.

ET

AL.

Translocations affecting the band 19q13 have been reported in chronic lymphocytic leukemia (Ueshima et al., 1985) and in glioma cells (Bigner et al., 1988; Speaks et al., 1987; Jenkins et al., 1989); it would be interesting to examine these tumor cells for possible alterations of the CEBP or DBP genes. The possibility that the CEBP gene could be involved in genetic alterations of cancer cells, like other transcription factor genes, seems reasonable, since CEBP can arrest cell growth and promotes terminal differentiation (Umek et al., 1991). With regard to the TCFl gene (encoding the HNFl/ NFB-1 factor), our assignment to human chromosome 12 is in agreement with the results of Bach et al. (1990), who also localized the mouse gene to chromosome 5, band F, thereby defining a new segment of homology between human chromosome 12 (q24.3) and mouse chromosome 5 (F). Our results indicate that this homology extends to a region of rat chromosome 12. This chromosome segment is thus distinct from the segment containing the synteny group conserved on human chromosome 12 and rat chromosome 7; this group comprises the retinoic acid receptor gamma gene (RARG, 12q13), the transcription factor Spl gene, and the phenylalanine hydroxylase gene (PAH, 12q22-q24.2) (Fulchignoni-Lataud et al., 1990; Levan et al., 1991; Mattei et al., 1991; Szpirer et al., 1991b) and is split in the mouse, on chromosomes 10 (Pub) and 15 (Rar-g and Spf) (Ledley et al., 1988; Mattei et al., 1991; Saffer et al., 1990). While this paper was in preparation, Weidner et al. (1991) and Fukuyama et al. (1991) independently reported that the HGF gene maps to human chromosome 7 (band q21). Our result agrees with these reports. It is striking that the HGF gene is located on the same chromosome as the gene that codes for the HGF receptor, namely, the MET oncogene (Cooper et al., 1984; Bottaro et al., 1991; Naldini et al., 1991).

FIG. ‘7. Localization of the rat HGF gene. Autoradiogram Southern blot of BamHI-digested DNA: mouse (MI, rat (RI, mouse X rat hybrids (LB150.1, LB210.1, and LB251).

of a and

CHROMOSOMAL

LOCALIZATION

Human chromosome 7 and rat chromosome 4, bearing the HGF gene, are already known to carry a conserved synteny group (containing the IL6, EPO, PGYI, and TCRB genes); in the mouse, this group is split into two parts, located on chromosomes 5 (IL6, Epo, Pgyl) and 6 (Tcrb) (Nadeau and Reiner, 1989; Levan et al., 1991, and references therein). ACKNOWLEDGMENTS We thank U. Schibler and S. McKnight for the kind gift of the DBP and CEBP probes, respectively. This work was supported by the Fund for Scientific Medical Research (FRSM, Belgium), the “Communaute Francaise de Belgique” (Action de Recherche Concert&e), the Belgian program on interuniversity attraction poles initiated by the Belgian State-Prime Minister’s Office-Science Policy Programming, the CGER-ASLK (Brussels), by the Swedish Cancer Society, the Erik Philip-Sorensen Foundation, the Trygger Foundation, the IngaBrittand Arne Lundberg Research Foundation, CANCIRCO, BioViist (Gothenburg), and by the Erna and Victor Hasselblad Foundation (Gothenburg and Brussels). C.S. is Research Director of the National Fund for Scientific Research (FNRS, Belgium).

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Feinberg, A., and DNA restriction 13’7: 266-267. Frain, M., Swart, and Cortese, R.

Vogelstein, fragments

M., Lichtsteiner, a novel member transcriptional

S., Falvey, E., and of the C/EBP gene famactivator protein. Genes

B. (1984). A technique to high specific activity.

G., Monaci, P., Nicosia, (1989). The liver-specific

CEBP,

Bl contains 59: 145-157.

for radiolabeling Anal. Biochem.

A., Stampfli, transcription

S., Frank, factor

R., LF-

DBP.

TCFl,

a highly

299

HGF

diverged

Homeobox

DNA

binding

domain.

Cell

Friedman, A., Landschulz, W., and McKnight, S. (1989). CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells. Genes Dev. 3: 1314-1322. Fukuyama, R., Icbijoh, Y., Minoshima, S., Kitamura, and Shimizu, N. (1991). Regional localization of the hepatocyte growth factor (HGF) gene to human chromosome 7 band q21.1. Genomics 11: 410-415. Fulchignoni-Lataud, M.-C., Weiss, M. C., Szpirer, C., and Levan, G. (1990). Assignment of the rat genes coding for phenylalanine hydroxylase (PAH), tyrosine aminotransferase (TAT), and pyruvate kinase (PKL) to chromosomes 7, 19, and 2, respectively. Cytogenet. Cell Genet. 53: 172-174. Gherardi, factor:

E., and Stoker, M. (1991). Hepatocyte Mitogen, motogen, and Met. Cancer

Islam, M. Q., and Levan, proved quality G-bands 127-130.

G. (1987). in routine

growth factor-scatter Cells 3: 227-232.

A new fixation procedure for imcytogenetic work. Hereditas 10’7:

Islam, Q., Platz, A., Szpirer, J., Szpirer, C., Levan, G., and Mannervik, B. (1989). Chromosomal localization of human glutathione transferase genes of classes, mu and pi. Hum. Genet. 82: 338-342. Jenkins, R. B., Kimmel, D. W., Moertel, C. A., Schultz, C. G., Scheithauer, B. W., Kelly, P. J., and Dewald, G. W. (1989). A cytogenetic study of 53 human gliomas. Cancer Genet. Cytogenet. 39: 253-279. Johnson, Growth

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Cell

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and assigned

scatter factor gene (HGF).

By means of somatic cell hybrids segregating either human or rat chromosomes, we determined the chromosome localization of three genes encoding transc...
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