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Common and Individually Specific Chromosomal Characteristics

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Common and Individually Specific Chromosomal Characteristics [CANCER RESEARCH 36, 398-404, February 1976] Common and Individually Specific Chromosomal Characteristics of Cultured Human Melanoma1 Peter B. McCulloch,2 Peter B. Dent, Paula R. Hayes, and Shuen-Kuei Liao Hamilton Clinic, Ontario Cancer Treatment and Research Foundation [P. B. M., P. B. D., P. R. H., S. K. L.], and Departments of Medicine [P. B. M., P. R. H.] and Pediatrics [P. B. D. , 5. K. L.J, McMaster University, Hamilton, Ontario, Canada SUMMARY any histological class of tumor. However, with the advent of individual chromosome identification, this whole area ne Since individual chromosomes can be accurately identi quires further study. fied by new banding techniques, atebnin fluorescence was used for chromosome analysis in six cell lines and two MATERIALS AND METHODS primary outgrowths derived from human malignant mela noma. Gross aneuploidy was seen in all specimens, but Eight different cultures obtained from human malignant each culture contained at least 1 distinctive marker chromo melanoma were studied. Their sources, individual chromo some specific for that cell line in 87 to 100% of metaphases. somal characteristics, and modal distribution of 50 meta One of the primary explants contained a marker that was phases from each culture are summarized in Table 1. demonstrable in fresh tissue and persisted through 2 weeks M-6 and 73-61 were primary explants established from of culture. The same marker was found in all metaphases metastatic malignant melanomas in our laboratory. The tis from 2 different metastases, but skin fibroblasts from the sue was minced and trypsinized. Some cultures were ob same patient had a normal chromosome complement. tamed from single cell suspensions, while others grew out No common marker for human melanoma was found, but from small fragments under glass coven slips. Samples from in 6 of the 8 cultures the most frequently found marker was these primary outgrowths were taken at various times for formed by a brightly banded chromatid addition. Relative cytogenetic studies. polysomy for Chromosome 7 was found in 7 of the 8 All 8 cultures were grown as monolayers in Eagle's mini cultures and, for Chromosome 22, in 5 of the 8 cultures. The mum essential medium with Hanks' balanced salt solution frequency of polysomy of Chromosomes 7 and 22 was signif containing 4 mM L-glutamine, 10 to 20% heat-inactivated icant at the 5% level. fetal calf serum, 100 @tgofstreptomycin sulfate per ml, and 50 units of penicillin G pen ml at 37°ina humidified atmos phene of 5% CO2in air. For chromosome analysis, Colcemid INTRODUCTION was added at a final concentration of 1.0 @g/ml2hr before harvesting. The cells were treated with 0.075 M KCI for 30 The utilization of specific staining techniques produces mm and fixed in methanol:acetic acid (3:1, v/v). The slides distinctive banding patterns that allow precise identification were flame dried and stained with 0.5% atebnin according to of individual human chromosomes (3). In the study of neo the method of Lin et a!. (10). The slides were scanned and plasms, these banding techniques disclose abnormalities metaphases were photographed with a Carl Zeiss fluones that were previously hidden by uniform staining. cent microscope using dark-field ilium ination. In our laboratory we have established and are maintaining From each culture, 45 to 55 metaphases were photo several melanoma cell lines to study patient-specific and graphed. Ten kanyotypes were made and the other 35 to 45 tumor-specific immunity (8). Since these lines show consid photographs were scanned for chromosome markers. enable morphological heterogeneity, these chromosome The total number of copies of each normal autosome was studies were undertaken to characterize the lines so that ascertained from the 10 karyotypes to detect any constant our immunological investigations can be performed on pure nullisomy on polysomy (Table 3). For statistical analyses the cultures from a defined origin. frequency of each autosome was ranked for each culture. Many chromosomal abnormalities have been recorded in The degree of polysomy of each autosome was then ana fresh and cultured human cancers, but, with the exception lyzed according to the formula: (rank total —mean rank) ÷ of the Philadelphia chromosome in chronic myelocytic Ieu S.D. (7, 16). Values greaten than 2.95 are significant at the kemia, no specific chnomosomal marker has been found for 5% level. RESULTS ‘Supported by grants from The Ontario Cancer Treatment and Research Foundation. This is Paper 2 of the series “CharacterizationofHuman Malig nant Melanoma Cell Lines,―bythe same authors. The marker chromosomes described for each line (Tables 2 To whom requests for reprints should be addressed, at Ontario Cancer 1 and 2) and shown in the karyotypes (Figs. 1 to 3) were Treatment and Research Foundation, Hamilton Clinic, 711 Concession Street, Hamilton, Ontario, Canada L8V 1C3. seen in oven 50% of the metaphases examined. Other Received August 21, 1974; accepted November 6, 1975. marker chromosomes did occur in each cell line but were 398 CANCER RESEARCH VOL. 36 Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 1976 American Association for Cancer Research. Chromosomes in Human Melanoma Table 1 Summary of the lines and primary outgrowths studied fre Designa designa quency marker Modal chro- of modal (9k)M-1Dr.tionObtained fromOriginal tionSex of donorHighestchromosomeRangeofchromosomenos.Frequencymosome no. no. 60NewJ. Fogh,RPMI-5966Unknownmar 2, lp+36—10053 to 57 YorkM-2Dr. 20NewJ. Fogh,RPMI-4445Unknownmar 637—7557 40M-3Dr. York66 to 70 64DenverM-4Dr. G. Moore,RPMI-8342Male4q+33-9053 14Denver86G. Moore,RPMI-7272Femalellq+ , llq++38—10046 10M-5Dr. 48Denver.M-6OurG. Moore,RPMI-8322Male4q+33—10053 distributionM-7Dr. laboratoryCaCI 73-36Femaleip 50—152Random 30Houston73-61OurM. Romsdahl,LeCa Strl9-4Male2q+38—7266 laboratoryCaCI 73-61Male5q+38—10046 14 87 10 Table 2 Metaphases High-fre containing quency the marker Culture markers (%) Description of marker M-1(RPMI-5966) mar 2 97 del(3)(p21) with terminal pale staining band (p21) elon gated lp+ 92 Chromosome 1 with bright chromatid addition 12p+ 90 Chromosome 12 with bright chromatid addition mar 1 87 Large metacentnic, with atypical banding M-2 (RPMI-4445) mar 6 87 Resembleschromosome18but haselongated palestain ing p arms mar 5 82 Large acrocentric, with banding unlike any human chro mosome mar 4 78 Large metacentric with atypical banding (differs from mar 1) mar 3 76 q arm of Chromosome 1 with shortened atypical banding of p arm M-3 (RPMI-8342) 4q+ 100 Chromosome 4 with bright chromatid addition “mini―11 82 Typical banding of Chromosome 11 , but smaller in size; possibly an isochromosome of the short arms of Chro mosome 12 17q/lOq 30 C-group size, made up by the long arms of Chromosome 17 attached at the centromere to the long arms of Chromosome 10 M-4 (RPMI-7272) llq+ 66 Chromosome 11 with chromatid addition consisting of 1 bright band llq++ 68 Chromosome 11 with 2 bright bands on the chromatid addition M-5 (RPMI-8322) 4q+ 100 Sameas in M-3 “mini―11 58 Sameas in M-3 17q/lOq 70 Same as in M-3 M-6 (CaCI73-36) 1p— 100 del(1)(p22),chromosome1 with 2/3of p arm deleted M-7 (LeCa Str 19-4) 2q+ 100 Chromosome2 with chromatid addition mar 9 92 Large acrocentric (differs from mar 5 in M-2) lp+ 88 Chromosome 1 with chromatid addition (differs from lp+ in M-1) mar 7 86 Large submetacentric with atypical banding mar 8 83 Long arm of Chromosome 3 attached at the centromere to a pale-stainingshort arm of uncertain origin 73-61(CaCI73-61) 5q+ 100 Chromosome 5 with chromatid addition present in less than 30% of the metaphases and were there- nomenclature defined at the Paris Conference on Standard i fore not useful in distinguishing the culture from another. zation in Human Cytogenetics (1971) (12). Whenever the origin of the marker chromosome could be M-1 (RPMI-5966). This is a slightly melanotic line estab determined, the marker chromosome was described by the lished oven 10 years ago at Roswell Park Memorial Institute FEBRUARY 1976 399 Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 1976 American Association for Cancer Research. P. B. McCullochetal. from a human malignant melanoma. Metaphases from the Two other common markers were found in 30 to 82% of 1st to the 4th passage in our laboratory were studied. It has the metaphases in both of these lines (Table 2). The kanyo a moderately sharp, hyperdiploid mode with 60% of the types from both of these cell lines showed polysomy for the metaphases examined ranging between 53 to 57 chromo normal Chromosomes 7 and 22 in the highest frequencies somes. Four different markers were seen in 87 to 97% of the (Table3). metaphases examined. They are specific for this cell line M-4 (RPMI-7272). This is an amelanotic cell line estab and are described in Table 2 and seen in Fig. 1. Polysomy lished from a female patient and maintained in continuous for the normal Chromosome 22 was most frequent in the 10 culture for approximately 2 years before our studies. The karyotypes from this line (Table 3). 4th and 5th passages in our laboratory were studied. The M-2 (RPMI-4445). This is an amelanotic line established chromosome number was bimodal with 1 peak at 46 and a over 10 years ago from a human malignant melanoma at 2nd peak at 86. All of the 50 metaphases examined from this Roswell Park Memorial Institute. Metaphases from the 2nd line contained an abnormal Chromosome 11 with either 1 on and 6th passages in our laboratory were studied. The chro 2 bright bands added to the lower arm (Fig.
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