The fra(X) chromosome was detected in 5 samples of amniotic fluid cells in a series of 23 pregnancies at risk. The prenatal results were confirmed in 2 male abortuses, one with a relatively high and one with a very low frequency of expression in both amniocytes and fetal tissue. In a third male fetus with low expression in amniocytes, the fra(X) was not detected in the fetal tissues tested. In another male with low expression in amniocytes the fra(X) was not detected after birth. In one female with a low expression in amniocytes, a very high frequency (28%) was detected in cord blood after birth. Low expression of the fra(X) was found in a 4-year-old normally developed girl, where the prenatal results had been negative. In 4 males and 4 females the negative prenatal diagnoses were confirmed after birth. This study indicates that prenatal diagnosis of the fragile X after amniocentesis may be complicated, either due to technical problems related to the use of amniotic fluid cells, or due to genetic heterogeneity, or both. Part of this heterogeneity could be due to the existence of normal male transmitters. Also, it seems that the frequency of expression in amniocytes from female carriers can not be used for the prediction of the frequency in blood after birth.

Amniocentesis↗

PubMedDate not supplied

Restricted number of chromosomal regions implicated in aetiology of human cancer and leukaemia.

It has been known since the days of Boveri that neoplasia is associated with chromosomal aberration. The introduction, some 10 years ago, of chromosome banding techniques provided the impetus for the description of an immense number of such aberrations, and for the localization to individual chromosome bands of the breaks underlying the aberrations. Hypothetically, the breaks should comprise two essentially different kinds: primary breaks that are actively involved in the malignant development, and secondary breaks, coincidental to this process. In the search for a possible method to identify primary breaks in human cancer, I selected from the catalogue of chromosome aberrations now available those cases that had one single structural aberration as their sole deviation from normality. I report here that the breakpoints thus specified affect a surprisingly limited number of chromosomal regions, and conclude that these regions contain genes of prime importance to cancer development.

Chromosome Aberrations↗

PubMedDate not supplied

NRAS mutations are rare in acute myeloid leukaemias with t(8;21) or inv(16).

Using PCR and direct sequence methodology, 19 haematologic malignancies with trisomy 8, 18 with t(8;21)(q22;q22) and 8 with inv(16)(p13q22) were screened for NRAS mutations. Of the 45 samples analyzed, 4 (9%) had a mutation; both wild-type and mutated alleles were observed in these 4 cases. Three of the mutations (involving codons 12 and 13) were found in the trisomy 8 group and 1 (codon 61) among the inv(16) samples. No specific clinical similarities were found in the 3 patients with +8 and NRAS mutation. By analyzing two sequential samples from the patient with inv(16) and NRAS mutation, it was shown that the mutation had occurred after the inversion. Since no NRAS mutations were detected among the t(8;21) samples and only 1 was found in the inv(16) group, we conclude that acute myeloid leukaemias with t(8;21) or inv(16) generally arise and progress without the involvement of NRAS mutations.

Acute Disease↗

PubMedDate not supplied

Cytogenetic analysis in the examination of solid tumors in children.

Although pediatric solid tumors are cytogenetically less well characterized than childhood leukemias, an understanding of the role of chromosomal changes in the development of these neoplasms is emerging. The major clinical importance of chromosome analysis today is diagnostic. Especially in small cell round cell tumors of childhood, the unique karyotypic patterns that characterize some of the differential diagnostic entities make it possible to determine with a high degree of certainty which type of cancer the child has. Molecular studies have revealed that almost all retinoblastomas show homozygous loss of function of the RB1 gene in 13q14. At the cytogenetic level, however, aberrations of 13q are seen in less than 25% of retinoblastomas; instead, the presumably progression-related i(6p) and aberrations leading to gain of 1q predominate, each being present in one-third of the tumors. Twenty percent of cytogenetically aberrant Wilms' tumors show structural rearrangements, often deletions, of 11p13 and 11p15, where the WT1 and WT2 genes map. Other frequent changes are trisomy 12 and duplication of 1q. The most common (80%) cytogenetic abnormality in neuroblastoma is loss of distal 1p, a chromosome segment thought to harbor at least two tumor-suppressor genes of importance in tumorigenesis. Double minute chromosomes or homogeneously staining regions are present in one-third of all neuroblastomas and are associated with MYCN amplification. Loss of 1p material or MYCN amplification predicts a poor outcome. The most common (30%) chromosomal aberration in primitive neuroectodermal tumors of the central nervous system is i(17q). The formation of this isochromosome may help inactivate a tumor-suppressor gene located distal to the TP53 locus on 17p. No specific chromosome abnormality has been detected in gliomas, but monosomy 22 and rearrangements leading to loss of 1p and gain of 1q are recurrent. Few hepatoblastomas with chromosomal changes have been reported, but several potential primary aberrations have been described, including +2, +20, and duplication 8q. In Ewing's sarcoma, t(11;22)(q24;q12) is the primary aberration, with trisomy 8 and gain of 1q being frequent secondary changes. Fibrosarcomas in children often carry only numeric aberrations, especially trisomy for chromosomes 11, 20, 17, and 8. Most osteosarcomas are cytogenetically complex, and no specific abnormality has been detected; the single most common change is loss of chromosome 13, which is observed in half the tumors. In contrast, the low-malignancy parosteal osteosarcomas often display supernumerary ring chromosomes as the sole karyotypic deviation. The cytogenetic profiles of rhabdomyosarcomas differ among the various morphologic subtypes.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗

PubMedDate not supplied

Chromosomes, genes, and cancer.

For over 100 years, scientists have been investigating the role of genetic change in neoplasia. Dr. Felix Mitelman, a Professor in the Department of Clinical Genetics at the University Hospital in Lund, Sweden, describes the progression in thought and technology that has led to the identification and characterization of genetic changes leading to cancer at a chromosomal and molecular level.

Animals↗

PubMedDate not supplied

The significance of karyotypic changes in human neoplasia.

Explore the source record for details and available documents.

Chromosome Aberrations↗