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Biomedical subjects

B Dutrillaux

Publications and source records attributed to B Dutrillaux.

At least 235 records · Page 13Linked to original sources
PubMed1990

Proto-oncogene amplification and homogeneously staining regions in human breast carcinomas.

Cytogenetic studies on fresh human breast cancers revealed that homogeneously staining regions (HSRs), which are assumed to represent DNA amplification, are observed in almost half of the cases. To search for a possible relationship between HSRs and proto-oncogene amplification, 16 proto-oncogenes, including ERBB2, were studied by Southern blot analysis in four tumors with two or three HSRs, and in three tumors without HSRs. Only four proto-oncogenes were found to be amplified in at least one tumor each: HST and INT2 (x3), MYC (x2-3), and FES (x greater than 10). The large sizes of the HSRs, which each corresponded to several percent of the haploid genome, were hardly compatible with the low rate of amplification, except for FES and then only if a large adjacent segment was co-amplified. This incomplete correlation was demonstrated by in situ hybridization, using biotinylated probes, which showed fluorescent spots on only one HSR for FES in one tumor and for INT2 in another one. Our results indicate that most of the large amplifications corresponding to HSRs do not involve the proto-oncogenes usually studied in breast cancer. The large amplification of FES, detected in one tumor, may be coincidental.

Blotting, Southern↗
PubMed1990

Cytogenetics of colorectal adenocarcinomas.

The occurrence of nonrandom chromosomal anomalies in colorectal adenocarcinomas could be demonstrated from the cytogenetic study of 100 cases. The most frequent changes are a rearrangement of chromosome 17, leading to the loss of its short arm and a loss of one chromosome 18. Three types of tumors with abnormal karyotypes can be defined. First are the monosomic-type near-diploid tumors (MD), characterized by a monosomy of both 17p and chromosome 18 mostly associated with other recurrent monosomies. In two of three cases, one or several minor derived polyploid subclones are also observed. Second are the monosomic-type polyploid tumors (MP), which have a pattern of chromosome imbalance very similar to that of MD tumors. They derive from MD tumors by endoreduplication followed by complete disappearance of the original MD clone. Third are the trisomic-type tumors (TT), which lose either 17p or chromosome 18 or none, most of the anomalies being gains of entire chromosomes. These TT tumors never undergo endoreduplication. In addition, seven tumors with normal karyotypes were found and may constitute another category (NT). A nonrandom distribution of these tumor types in relation to tumor site was observed, since in the distal colon, TT and NT tumors are underrepresented and endoreduplications are significantly more frequent. The level of chromosomal mutagenesis is two- to threefold higher in MD and MP than in TT tumors. More than 95% of the rearrangements are unbalanced, and most of them result from breakpoints located in juxtacentromeric heterochromatin. A good correlation is found between our results and the available molecular data on allelic losses. The involvement of recessive tumor suppressor genes in colorectal tumorigenesis and the possible relationship between chromosomal imbalances and deviations in metabolic pathways is described.

Adenocarcinoma↗
PubMed1990

Cytogenetic and molecular approaches of polyploidization in colorectal adenocarcinomas.

We present the cytogenetic analysis of 23 cases of polyploid colorectal adenocarcinomas. We took advantage of the high intratumoral heterogeneity of the karyotypes to identify clones, subclones, and cell-to-cell variations. This allowed us to reconstruct the chromosomal evolution of each tumor and to propose a schema of the chromosomal changes in relation to the endoreduplication process. All but one case were characterized by a relative deficiency of chromosomes 17p and 18. Other deficiencies affecting the late-replicating X, and to a lesser degree, 1p, 5q, 14, 15, 8p, 10, 21, and 4, and excesses affecting the early-replicating X, 8q, 13, 16, 17q, and 11 were frequently associated. This pattern of imbalances is very similar to that of the monosomic type previously described in near-diploid tumors. The pattern of the 23rd tumor corresponded to those of the trisomic type tumors. These data largely confirm the existence of two distinct processes of chromosomal evolution in colorectal adenocarcinomas, with a strong tendency to undergo endoreduplication for the monosomic type near-diploid tumors. To correlate cytogenetic and molecular data, allelic losses analyses were investigated for probes of chromosomes 17p and 18. In all 12 informative tumors, a loss of heterozygosity for probes of the short arm of chromosome 17 indicated the occurrence of a rearrangement of chromosome 17 before the endoreduplication. The same was true for allelic losses for probes of chromosome 18 found in 11 of 12 informative tumors. The correlation between cytogenetic and molecular data is thus excellent and indicates that losses of 17p and 18 are early events in the tumor process.

Adenocarcinoma↗
PubMed1990

Biclonal chromosome evolution of chronic myelomonocytic leukemia in a child.

A monosomy 7 was first detected in a 6-month-old boy with a chronic myelomonocytic leukemia. After etoposide treatment, relapse occurred after 29 months, with transformation of the disease into an acute myeloblastic leukemia. After bone marrow transplantations, two abnormal clones were found in marrow cells: 45,XY,-7,del(12)(p11p12)(66%), and 45,XY,-7,t(3;12)(q26;p12)(33%). Several karyotypic studies performed until the terminal phase exhibited the persistence of these two clones in the same proportion, although both independently acquired additional and often similar anomalies. The clone with t(3;12) acquired der(7),der(11),der(17),der(8),der(10),-5,-20, and the clone with del(12p), del(5q),der(4),der(8),der(10),der(17),-5,-20. The anomalies in 12p12 appear to represent an important although secondary event of the neoplastic process. The other anomalies may correspond to either those of a secondary acute nonlymphocytic leukemia, since they occurred after treatment by etoposide and alkylating agents, or to the natural evolution of myelomonocytic leukemia.

Bone Marrow↗
PubMed1990

Establishment and characterisation of a new tumorigenic cell line with a normal karyotype derived from a human breast adenocarcinoma.

A new cell line (CAL51) was isolated from a malignant pleural effusion of a woman with metastatic breast cancer. These cells grow in continuous culture and exhibit the morphological, ultrastructural and immunohistochemical features of epithelial cells of mammary origin. They are tumorigenic in nude mice and clone in soft agar. Oestrogen receptors are not detected. CAL51 consists of a homogeneous population of cells with normal chromosomes even after the use of high resolution banding. Cytogenetic analysis of the cells from the tumour induced by CAL51 in the nude mouse confirmed the normality and the stability of the karyotype. All breast cancer cell lines established to date present abnormal karyotypes; CAL51 cell line may be more informative than cell lines with aberrant karyotypes for investigating essential genetic differences between normal and malignant mammary gland cells.

Adenocarcinoma↗
PubMed1990

Revision of the chromosome anomalies of the T-cell malignant cell line peer.

A high resolution chromosome banding method was applied to define the karyotype of the PEER cell line. It was found significantly different from that previously described, and can be characterized as follows: 46,XX,-4, del(5) (q21q23), del(6)(q14q22), del(9)(p12p21), i(9p), +der(4) rea(4) involving a large duplication of 4q. The cell cycle duration varies in relation to the time after splitting, slow from 0 to 48 h and faster from 48 to 96 h. The average time found was 25 h with durations of 6 and 15 h for G2 and S-phases, respectively. This variable cell cycle led us to change the conditions of BrdU incorporation to obtain a convenient R-banding. According to our own experience, this can be transposed to many other malignant cells to obtain a high resolution chromosome banding.

Bromodeoxyuridine↗
PubMed1989

Preservation of chromosome and DNA characteristics of human colorectal adenocarcinomas after passage in nude mice.

Twenty-seven human colorectal adenocarcinomas were implanted s.c. into nude mice. A comparative study of chromosomes and DNA between fresh tumor (FT) and xenografted tumor cells (XT) could be performed in 9 cases. Losses or deletions were consistently found in FTs as well as in XTs, particularly on chromosomes 17 and/or 18. This was correlated with loss of heterozygosity for these chromosomes. Comparison between corresponding FT and XT karyotypes showed great similarities. However, the tendency toward polyploidization, which exists in FTs, appeared to be more pronounced in XTs. Passage in nude mice makes it possible to repeat cytogenetic analyses in order to obtained interpretable metaphases. Xenografting not only increases the number of tumorigenic cells, but also eliminates human normal stromal or blood cells and gives unambiguous data on allelic loss.

Adenocarcinoma↗
PubMed1989

Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer.

A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Cytogenetic study on eleven cutaneous neoplasms and two pre-tumoral lesions from Xeroderma pigmentosum patients.

Eleven independent tumors (5 basa-cell carcinomas, 5 squamous-cell carcinomas and 1 malignant melanoma), 2 pretumoral lesions and one common nevus, developing in the skin of 10 unrelated XP patients were cytogenetically analyzed. No specific chromosomal changes were observed. Two features were relevant, however: emergence of several independent clones and over-involvement of telomeric and centromeric regions in the formation of chromosomal rearrangements. Jumping translocations were observed in 2 squamous-cell carcinomas involving telomeric and centromeric regions.

Adolescent↗
PubMed1989

Jumping end-to-end dicentrics in a case of squamous cell carcinoma from a patient with xeroderma pigmentosum.

Cytogenetic studies of a skin squamous cell carcinoma from a xeroderma pigmentosum patient were performed at several passages. They show the existence of recurrent rearrangements: 53% were dicentrics, of which 67% were of the telomere-telomere type. The telomeric region of the long arm of chromosome 12 was the most involved (in 38% of dicentrics), followed by 22p. The origin of this type of jumping rearrangement and its possible role on cell proliferation are discussed.

Adolescent↗
PubMed1989

Chromosomal aberrations in lymphocytes of patients treated with melphalan.

Chromosome lesions detected in lymphocytes from 14 patients previously treated with melphalan, a bifunctional alkylating agent, have been analyzed on R-banded preparations. In comparison to controls, there was no significant increase of chromatid-type lesions, but chromosome-type lesions were quite frequent, affecting 21.5% of metaphases, on the average. Reciprocal translocations represent 54%, unbalanced translocations 15%, deletions 19% and inversions 6% of all rearrangements. Most of these would not have been detected without the use of chromosome banding. The distributions of affected chromosomes and chromosome bands were not random. Almost all imbalances resulting from rearrangements lead to losses but not to gains. The distribution of the abnormal chromosomes has been compared to that observed in controls and in in vitro experiments, and to the characteristic pattern of malignant cells from patients affected by secondary acute leukemia (ANLL).

Breast Neoplasms↗
PubMed1989

Increase of sister chromatid exchanges in excision repair deficient xeroderma pigmentosum.

The distribution of spontaneous sister chromatid exchanges (SCEs) was studied in PHA-stimulated lymphocytes from 15 patients affected by xeroderma pigmentosum (XP). The study of unscheduled DNA synthesis (UDS) in twelve of these patients showed that seven were deficient and five proficient. The number of SCEs in XP patient cells was higher than in those of 19 controls, and the distributions of SCEs per cell were significantly different. However, the results varied when XP patients were considered in relation to their UDS: the group of XP patients with proficient UDS did not differ, whereas the group of XP patients with deficient UDS was very significantly different from controls. The group not tested for UDS was similar to the deficient UDS group. The possible relationship between the increase of SCEs and the type of DNA repair defect is discussed.

Adolescent↗
PubMed1989

Detection of 1q polysomy in interphase nuclei of human solid tumors with a biotinylated probe.

A biotinylated probe (L23-21) specific for the 1q12 band of human karyotype was used to detect the 1q segment in interphase nuclei of breast and colon carcinomas. This probe was selected because trisomy or polysomy 1q is the most frequent chromosomal change observed in solid tumors. This method enables cancerous cells, including near-diploid ones carrying an unbalanced rearrangement of 1q, to be easily identified.

Biotin↗
PubMed1989

Chromosomal aberrations induced by low-dose gamma-irradiation. Study of R-banded chromosomes of human lymphocytes.

The effect of low-dose (0-0.5 Gy) gamma-radiations was studied on R-banded chromosomes from lymphocytes of healthy donors of various ages. In cells from newborns, an increase of chromosome damage roughly proportional to the dose was found. In lymphocytes from young adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults not even at 0.2 Gy. The difficulty in detecting aberrations in lymphocytes from adults is largely due to a considerable background of chromosomal anomalies which should be borne in mind in dosimetry studies. The rate of induction largely depends on the types of rearrangements. One-break terminal deletions are efficiently induced at 0.1 and 0.2 Gy and are the best indicators of exposure at these doses. At 0.5 Gy, the frequencies of 2-break lesions, i.e., dicentrics and reciprocal translocations, increase, whereas that of deletions decreases.

Chromosome Aberrations↗
PubMed1989

The chemotherapeutic drug melphalan induces breakage of chromosomes regions rearranged in secondary leukemia.

A cytogenetic study is reported on the lesions induced in vitro by melphalan, a currently used anticancer drug. The distribution of 2166 breakpoints shows that they do not occur at random. There is a large excess of breaks in region q1 of chromosome 9 and R bands are significantly more affected than G-band-rich segments. Furthermore, some regions of chromosomes 5, 7, 11, and 17, which are the chromosomes usually rearranged and deleted in secondary leukemias, presumably induced by such treatments, are frequently affected. It is presumed that the frequent involvement of 9q1 largely reflects preexisting monostrand breaks. The frequent breakage of chromosomes 5, 7, 11, and 17 and of R bands in general, which are known to be G-C rich, may result from the preferential methylation of the O6 of guanine by melphalan.

Acute Disease↗
PubMed1989

Unusual karyotypic evolution in subacute myelomonocytic leukemia in two monozygotic twins.

A subacute myelomonocytic leukemia was diagnosed in 28-month-old cotwins. At this age, their spontaneously dividing cells had a normal karyotype. A few months later, after treatment with 6-mercaptopurine, the following karyotypes were observed: 50,XX, +X, +13, +19, +21 in one and 51,XX, +X, +X, +10, +19, +21 in the other. After bone marrow transplantation, both relapsed although they had received high doses of chemo- and radiotherapy. One developed a clone 46,XX,del(20q), which acquired other clonal rearrangements. The other child developed two different abnormal clones, both with unbalanced rearrangement of chromosome 13. Some of these clones may correspond to immature erythroblasts. The gain of chromosomes, especially for #13, which occurred independently in the cotwins by various mechanisms and at different periods during the disease, is very striking. It may indicate the existence of a strong selective advantage for trisomic 13 cells and may be related to the genetic constitution of the patients.

Bone Marrow Transplantation↗