Nurettin Basaran

The importance of genomic copy number changes in the prognosis of glioblastoma multiforme

Glial tumors are the most common tumors of the nervous system, affecting individuals at any age. Since understanding of the molecular pathologies underlying human gliomas is still very poor, the treatment and therefore prognosis of this malignancy could not yet be improved. In order to determine whether different glioblastoma-associated genomic aberrations may serve as prognostic markers in combination with histopathological findings, 20 primary glioblastoma multiforme tumors were screened by comparative genomic hybridization, and the results were compared with histopathological and clinical features. All tumors showed genomic copy aberrations detected by comparative genomic hybridization. Regional and numerical increases in chromosome 7 copy number were the most frequently seen abnormality (10/20 tumors), followed by loss of chromosome 10 (8/20). Both of these aberrations were associated with shorter surveillance time. Chromosome 12q amplification was detected in seven tumors. Loss of 17p, 1p, and 19q in combination was seen in three cases. One of them was a giant cell GBM, whereas the remaining two cases were still alive. Combination of chromosome 1p and 19q deletions was also seen in a case with long surveillance. According to the preliminary findings of this study, in addition to the EGFR gene, amplification of other genes on chromosome 7 and the deletion of PTEN gene and other cancer-related genes on chromosome 10 appeared important to the development of glioblastoma multiforme and were associated with poor prognosis, whereas the combination of chromosome 1p and 19q deletions seems to be an informative molecular marker for better prognosis. The clinical features and genetic alterations of primary and secondary glioblastoma multiforme should be compared in large series to clarify the effective prognostic markers; and further molecular analyses focused on chromosomes 7 and 10 will be very helpful for understanding the molecular mechanisms underlying the progression of glioblastoma.

The effect of consanguinity on the reproductive wastage in the Turkish population

Analysis of data from 56664 marriages in Turkey studied from 1970 to 1988 showed an overall rate of consanguineous marriages, of 21.25%, and increases in the rates of abortions, stillbirths, prenatal losses and neonatal deaths.

Dacryocystitis associated with osteopoikilosis

We report five members of a family with dacryocystitis associated with osteopoikilosis. The inheritance is autosomal dominant. Review of the literature revealed no other report of this kind of association. Osteopoikilosis must not be considered as a coincidental radiographic finding but as part of a systemic disorder.

Consanguineous marriages among parents of Down patients

In order to reveal if there is an effect on the genesis of meiotic‐ or early zygotic non‐disjunctions, data related to 1598 Down syndrome patients from 1578 families studied in five different genetic centers in Turkey are reported. Parental consanguinity and the inbreeding coefficient were found to be lower among patients of 21‐trisomics than in parents without Down offspring. It was concluded that available information does not support the presence of a “non‐disjunction gene” in man.

Effects of consanguinity on anthropometric measurements of newborn infants.

The effects of parental consanguinity on gestational age and birth measurements were evaluated on 2880 newborn infants. Consanguineous marriages were considered in three subgroups: first‐cousin, first‐cousin‐once‐removed and distant‐cousin marriages, versus non‐consanguineous marriages. Anthropometric parameters were weight, length, leg length, head, chest and mid‐arm values obtained within 24 h of birth. No significant differences were found concerning gestational age. Although anthropometric values were slightly less, especially in children from first‐cousin couples, the differences were insignificant for all groups. It was concluded that blood‐relationship alone does not affect such multifactorial traits.

A rare case: mosaic trisomy 22

A 9-year-old female child of healthy parents (mother: 43 years, father: 44 years) was referred to our center because of severe mental retardation. While pedigree analysis was not contributory, two older sibs were normal and healthy. Physical examination revealed facial dysmorphism, microcephaly and hyperflexibility of all joints. Her chromosome constitution showed a mosaic pattern; mos 46,XX[98]/47,XX,+22[2]. So skin biopsy was performed and mosaic trisomy 22 was confirmed with FISH analysis (46,XX[73]/47,XX,+22[27]). Physical features of this case seemed consistent with her mosaic constitution. This report would be a demonstrative example to show the significant contribution of FISH in states of mosaicism.

FISH analysis with locus-specific probes in sperm from two translocation carrier men

Meiotic segregation of normal and derivative chromosomes was analysed in sperm samples from two balanced reciprocal translocation carrier men by use of dual‐colour fluorescence in situ hybridisation (FISH) technique. The translocations were t(4;8)(p15;p12) and t(15;22)(q(23;q13.2), and the digoxigenin‐labelled FISH probes were specific to either the translocated or centric segments of the chromosomes involved in the translocations. A total of 1000 spermatozoa for each probe were analysed and the modes of segregation were described on the basis of signals in each sperm cell. The mean frequency of alternate and/or adjacent‐1 (adj‐1) segregation types was 69.47%, whereas they were 30.51 and 78.70% for the adjacent‐2 (adj‐2) and alternate/adj‐2 segregation types, respectively. This study illustrated that FISH is a valuable technique for analysing the meiotic segregation products of the heterozygotes in respect to aneuploidy risk.

Real effects of consanguinity

Sirs, Students of medical genetics are often in some conflict and difficulty in distinguishing the relative roles played by genetic and environmental factors in etiology. Lenz stresses: “Even in the case of disorders which are obviously determined exclusively by environment ... the proof of the lack of participation of hereditary factors, carried out by genetic methods, can be of importance” (Lenz 1963). And such is the case with our communication dealing with fetal wastage. There were 12 039 (21.25%) families with consanguinity against 44 625 (78.75%) families without (Bagaran et al. 1989). They were from 3 different cities in Turkey and we believe almost all of the subjects from both groups share socio-economic, cultural, ethnic and religious environments with very similar components. One would thus expect that environment acts in almost the same direction and to the same extent in both groups of families. To our best knowledge, there is no evidence that related individuals repond differently to noa-genetic factors. Yet we state that consanguinity exerts unfavorable effects through unfavorable genes not only upon fetal wastage but also upon neonatal losses, as is the case for a community such as Norway with an apparently better registration system and a society with a better controlled environment (Magnus et al. 1985). We, however, agree that we should pay more attention to the fact that several nongenetic agents cannot be underestimated concerning reproductive outcome. Dr. Jeppesen and Dr. Juul appreciate that the frequency of malformed babies born to a small group of immigrants in European countries, including Denmark, is another subject to be studied more carefully. The malformation frequency in Turkey seems not to be higher than reported for western populations (Akgit et al. 1988). So it appears imperative that the effects of consanguinity should be restudied to avoid biases before the rate of consanguineous marriages falls. Nurettin Bagaran