Pathology and genetics of tumours of the urinary system and male genital organs

Inheritance of a mutation at the Rb-1 locus, which has been mapped to band q14 of human chromosome 13, results in predisposition to retinoblastoma. Cloned DNA segments homologous to arbitrary loci of human chromosome 13 and which reveal polymorphic restriction endonuclease recognition sequences, have been used to look for somatic genetic events that might occur during tumorigenesis. A comparison of constitutional and tumour genotypes from several cases indicates that tumorigenesis may result from the development of homozygosity for the mutant allele at the Rb-1 locus. The homozygosity in these cases results from mitotic nondisjunction, resulting in loss of the homologous wild-type chromosome, or from a mitotic recombination event.

Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

The LNCaP cell line was established from a metastatic lesion of human prostatic adenocarcinoma. The LNCaP cells grow readily in vitro (up to 8 x 10(5) cells/sq cm; doubling time, 60 hr), form clones in semisolid media, are highly resistant to human fibroblast interferon, and show an aneuploid (modal number, 76 to 91) human male karyotype with several marker chromosomes. The malignant properties of LNCaP cells are maintained. Athymic nude mice develop tumors at the injection site (volume-doubling time, 86 hr). Functional differentiation is preserved; both cultures and tumor produce acid phosphatase. High-affinity specific androgen receptors are present in the cytosol and nuclear fractions of cells in culture and in tumors. Estrogen receptors are demonstrable in the cytosol. The model is hormonally responsive. In vitro, 5 alpha-dihydrotestosterone modulates cell growth and stimulates acid phosphatase production. In vivo, the frequency of tumor development and the mean time of tumor appearance are significantly different for either sex. Male mice develop tumors earlier and at a greater frequency than do females. Hormonal manipulations show that, regardless of sex, the frequency of tumor development correlates with serum androgen levels. The rate of the tumor growth, however, is independent of the gender of hormonal status of the host.

https://cancerres.aacrjournals.org/content/canres/43/4/1809.full.pdf

LNCaP model of human prostatic carcinoma.

https://www.cell.com/cell/pdf/0092-8674(84)90077-1.pdf

Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22

Devoilement des oncogenes cellulaires: strategies experimentales et definitions. Caracteristiques structurales. Phylogenese. Expressions. Fonctions. Familles d'oncogenes cellulaires. Linkages. Transduction par des retrovirus. Role des oncogenes cellulaires dans les cellules normales, dans la transformation maligne, dans la genese des tumeurs

Cellular oncogenes and retroviruses

N the inorphologic identification of chromosomes, the location of the I centromere is the most useful landmark, and one which is characterized by great constancy. It would seem that not much could be added to the definitions by E. B. WILSON (1928) of the locations on the chromosome of the centrornere or, in the terminology of that time, the spindle attachment: “Attachment of the chromosome to the spindle is commonly limited to a small area, and is of two general types, namely: (1) terminnl or telomitic and (2) non-ferminal or atelomitic, being in the former case at one end, and in the latter at some other point or points. Non-terminal attachment may be at the middle point (median) or at an intermediate point (submedian, sub-terminal). All gradations exist between these various cases;” (I.c., p. 130-131). In the acconipanying picture (l.c., Fig. 56, p. 132), here reprinted as Fig. l., the four locations of median, submedian, subterminal and terminal are represented, and, in addition, “lateral”, which corresponds to the modern term “diffuse centromere”. Nevertheless, at the present time, with the immense increase in research activity in mammalian cytology, the terminology of the centromeric position has become burdened by much obscurity and confusion. One cause of confusion is that different authors, and even the same author on different occasions, have used the terms median, submedian etc. with great amplitude, and it is often difficult to know in a specific case what each term signifies. Another cause of confusion is that a set of terms for chromosomes with specific centromeric positions, such as metacentric, acrocentric, telocentric, have come into wide usage without being clearly defined in relation to the positional terms median, submedian, subterminal and terminal. During the spring of 1963 the present writers exchanged epistolary

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1601-5223.1964.tb01953.x

Nomenclature for centromeric position on chromosomes

The chromosomes in human cancer and leukemia

Chromosomes in kidney, ureter, and bladder cancer.

Chromosomes were studied in the bone marrow and/or blood cells from 38 patients with acute myeloblastic leukemia (AML). The initial analysis with conventional Giemsa staining revealed that 16 of the 38 patients with AML studied had chromosomal abnormalities. The cells of these 38 patients (16 with abnormal karyotypes and 22 with normal karyotypes) were re-examined with Q- and G-banding techniques. Twenty-two patients with conventionally stained normal karyotypes did not show any abnormalities, even with banding techniques. Three cases had a common translocation between the long arm of No. 8 and No. 21, i.e., [t(8;21)(q22;q22)], the so-called prototypic karyotype. Two cases had a 45, XX,-21 karyotype; and three cases had trisomy of the long arm of chromosome No. 1. The banding patterns revealed that in two of the three latter cases, the presence of the trisomy of the long arm of No. 1 apparently occurred late in the disease. Therefore, it is possible that the trisomy of the long arm of No. 1 might bear a relationship to selective growth advantage of the leukemic cells in some cases with AML. The presence of extra No. 8 and No. 9 chromosomes and deletion of the long arm of No. 7, frequently reported in several leukemic disorders, were also found in the present cases, but with other chromosomal abnormalities. Chromosomes No. 6,No. 15,No. 19,No. 20, and X were not involved in any structural and/or numerical changes. The present data suggest that some chromosomal changes are nonrandom in AML and that further chromosomal studies may lead to a division of AML patients into subgroups on the basis of their karyotypes.

Chromosomes and causation of human cancer and leukemia. XVII. Banding studies in acute myeloblastic leukemia (AML).

The chromosome constitution of 62 papillary tumors and 75 invasive transitional cell carcinomas of the bladder has been examined. Of the 62 papillary tumors, 12 were benign and were found to be preponderantly diploid; 2 of these tumors recurred, however, and in each a few karyotypically abnormal cells were present on the original examination. The modal chromosome number in the 50 papillary cancers ranged in the diploid area (44 to 49 chromosomes) with the karyotypic picture being different from tumor to tumor. Of the 50 papillary cancers, 32 had 1 to 2 marker chromosomes. Twelve of the papillary tumors recurred; only 1 did not have a marker. Thus, the recurrence of the 11 papillary tumors with markers indicates that their presence may be of value in predicting the behavior of papillary cancers of the bladder. The chromosomal picture in the recurrent papillary tumors did not differ materially from the original one, although a slight modification in the chromosome number may occur. On the other hand, invasive transitional cell cancer of the bladder was accompanied by a large number of chromosomes and a relatively large number of marker chromosomes with many complicated karyotypic pictures. The presence of marker chromosomes in papillary cancers may be indicative of the likelihood of recurrence and/or progression of such tumors and should attract the attention of those involved in the care of patients with these cancers.

https://cancerres.aacrjournals.org/content/canres/37/8_Part_2/2950.full.pdf

Avery A. Sandberg

Papers

Nomenclature for centromeric position on chromosomes

The chromosomes in human cancer and leukemia

Chromosomes in kidney, ureter, and bladder cancer.

Chromosomes and causation of human cancer and leukemia. XVII. Banding studies in acute myeloblastic leukemia (AML).

Chromosome Markers and Progression in Bladder Cancer