SNRPN methylation patterns in germ cell tumors as a reflection of primordial germ cell development.

Studies examining altered imprinted gene expression in cancer compare the observed expression pattern to the normal expression pattern for a given tissue of origin, usually the somatic expression pattern for the imprinted gene. Germ cell tumors (GCTs), however, require a developmental stage-dependent comparison. To explore using methylation as an indicator of germ cell development, we determined the pattern of methylation at the 5' untranslated region of SNRPN in 89 GCTs from both children and adults. Fifty-one of 84 tumors (60.7%) (12/30 (40%) of cultured pediatric GCTs, 23/36 (63.9%) of frozen adult GCTs, and 16/23 (69.5%) of frozen pediatric GCTs, with five samples having results from both cultured and uncultured material) demonstrated a nonsomatic methylation pattern after dual digestion with XbaI, NotI, and Southern blot analysis. In contrast, only 2 of 18 (11%) control samples (16 non-GCTs and 2 normal ovaries) exhibited a nonsomatic pattern. In both cases, the result was shown to be due to copy number differences between maternal and paternal homologs, unlike the GCTs in which there was no evidence of an uneven homolog number. A comparison of the data for only the gonadal GCTs and the control data showed a highly significant difference in the proportion of tumors with methylation alterations at this locus (P = 0.0000539). Since there is no published evidence of the involvement of SNRPN methylation changes in the development of malignancy, the data suggest that the methylation pattern of SNRPN in GCTs reflects that of the primordial germ cell giving rise to the tumor.

Chromosomes 1 and 12 abnormalities in pediatric germ cell tumors by interphase fluorescence in situ hybridization.

Chromosome studies of pediatric germ cell tumors (GCTs) show differences in abnormalities dependent on age, sex, tumor location, and histology. Previous studies suggest that loss of 1p is associated with a malignant phenotype, while amplification of 12p, a common finding in adult testicular GCTs, is uncommon in pediatric GCTs. Fifty-three pediatric GCTs were analyzed for 1p36 loss and 12p amplification by G-banding and dual-color interphase FISH with probes for the centromere and short arm of chromosomes 1 or 12. Twelve tumors with loss of 1p36 were identified. No deletion was detected in tumors with nonmalignant histology, such that there was a significant association of 1p loss with malignancy in these tumors (P = 0.00115). Five of 18 tumors from male patients had amplification of 12p, consistent with G-band results. Combined analysis of our data with those in the literature revealed a significant correlation of 12p amplification with patient age (P = 0.000196). Amplification of 12p was only seen in one of 35 tumors from female patients. Five female GCTs had numerical abnormalities of chromosome 12, and two tumors showed complete lack of 12p. This spectrum of abnormalities differs from what is seen in the male tumors, providing further evidence for different etiologies of GCTs between the sexes.

Chromosome abnormalities of eighty-one pediatric germ cell tumors: sex-, age-, site-, and histopathology-related differences--a Children's Cancer Group study.

The chromosomes of 81 pediatric germ cell tumors (GCTs) were analyzed as part of two clinical treatment trials, INT-0098 and INT-0097, conducted by the Children's Cancer Group. The analysis of chromosome results showed differences with respect to sex, age, tumor location, and histology. Sixteen of 17 benign teratomas of infants and children less than 4 years old and from gonadal and extragonadal locations were chromosomally normal. Twenty-three malignant GCTs from gonadal and extragonadal locations of the same age group were endodermal sinus tumors and varied in their karyotypic findings. The most common abnormalities were gains of 1q and chromosome 3. Of eight benign ovarian teratomas from older girls, five with normal G-banded karyotypes were determined to be homozygous for Q-band heteromorphisms, suggesting a meiosis II error. Among the 12 malignant ovarian GCTs from older girls, the common abnormalities were loss of 1p/gain of 1q, +3, +8, +14, and +21. Four of eight extragonadal tumors from older boys demonstrated +21; one had +X. Five of the eight had associated constitutional chromosome abnormalities, including one trisomy 21 and three with Klinefelter syndrome. The testicular GCTs of adolescents had abnormalities resembling those found in adult testicular GCT, including near-triploidy, loss of chromosomes 11, 13, and 18, and gain of chromosomes 7, 8, the X chromosome, and an isochromosome 12p. The gain of an isochromosome 12p was only frequent in the tumors from adolescent boys. Deletion of 1p/gain of 1q and +3 were the most common abnormalities among the malignant tumors from both sexes.

Clinical outcomes of four patients with microdeletion in the long arm of chromosome 2.

We present clinical outcome, through several years of follow-up, of 4 mentally retarded patients, each with a small interstitial deletion in the long arm of chromosome 2, within a region on which clinical reports are infrequent. Our patient 1 was found to have del(2)(q22.3q23.3); patients 2 and 3, del(2)(q23.3q24.2); and patient 4, del(2) (q24.2q31). By comparison of our cases with each other and with those previously published with comparable interstitial deletion, we attempted to identify characteristic clinical findings. Short neck with excessive cervical skin was seen with monosomy of chromosome 2 bands q22.3-q23.3, while hypertrichosis and a peculiar high pitched cry were seen with monosomy of chromosome 2 bands q23.3-q24.2. As suggested by Moller et al. [1984: Hum Genet 68:77-86], a cleft between the first and second toes was seen with monosomy of chromosome 2 bands q24.2-q31. In addition, seizure disorder was present in patients 1 and 4 (with the more proximal and distal deletions, respectively).

Complex translocation [7;22] identified in an epithelioid hemangioendothelioma.

We describe a malignant epithelioid hemangioendothelioma arising in the back of a 45-year-old man with pulmonary and bone marrow metastases. Light microscopic and immunohistochemical features of this tumor are presented. Karyotyping revealed several clonal abnormalities: a complex unbalanced translocation [7;22] involving multiple breakpoints (confirmed by fluorescence in situ hybridization), a Robertsonian t(14;14), and loss of the Y chromosome. Monosomy for chromosome 11 was noted in a subset of the tumor cells. To our knowledge a karyotype has not been previously reported for this unusual vascular tumor.

X-autosome translocation with a 47,XXXY qs,t(9p-;Xq+) karyotype.

A male with a karyotype 47,XXXY qs,t(9p-;Xq+) was ascertained utilizing ASG-banding. The karyotype was repeated because the original diagnosis of Klinefelter syndrome (47,XXY) was inconsistent with many of the stigmata present. It is suggested that many karyotypes completed prior to the advent of banding techniques will be repeated in an attempt to provide more accurate diagnosis, describe more aberrations, and possibly establish new syndromes.