Intracranial Malignant Germ Cell Tumor and the Klinefelter Syndrome

Ja, Prall; McGavran, Loris; Bs, Greffe; Partington, Jonathan R.

doi:10.1159/000120962

Cited by 25 publications

(11 citation statements)

References 19 publications

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“…48,49 Furthermore, there have been single reports of CNS-GCTs in the presence of Klinefelter syndrome. [50][51][52] In our series of patients, we have no clinical data indicating constitutional Klinefelter syndrome. A previous FISH analysis of six suprasellar teratomas (age 2-25 years) revealed a high frequency of sex chromosomal abnormalities, with a normal constitutional karyotype in one analyzed patient.…”

Section: Discussionmentioning

confidence: 74%

Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization

et al. 2006

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The limited information available to date regarding the genetic alterations in germ cell tumors of the central nervous system has raised concerns about their biologic relationship to other germ cell tumor entities. We investigated fresh-frozen or archival tumor samples from 19 patients with central nervous system germ cell tumors (CNS-GCTs), including seven germinomas, eight malignant nongerminomatous germ cell tumors and four teratomas, using chromosomal comparative genomic hybridization to determine recurrent chromosomal imbalances. All 15 malignant CNS-GCTs and two of four teratomas showed multiple chromosomal imbalances. Chromosomal gains (median: 4 gains/tumor, range: 0-9 gains/tumor) were observed more frequently than losses (median: 1.6 losses/tumor, range: 0-6 losses/tumor). Gain of 12p, which is considered characteristic for germ cell tumors of the adult testis, was detected in 11 of 19 tumors and 10 of 15 malignant CNS-GCTs. In one tumor, gain of 12p was confined to an amplicon at 12p12, corresponding to the commonly amplified region on 12p. Other common gains were found on chromosome arms 1q and 8q (n ¼ 9, each). Among the chromosomal losses, parts of chromosome 11 (n ¼ 5), 18 (n ¼ 4), and 13 (n ¼ 3) were deleted most frequently. Notably, we observed no difference in the genetic profiles of germinomatous and nongerminomatous CNS-GCTs; however, the average number of imbalances was higher in the latter group. A meta-analysis comparing 116 malignant gonadal and extragonadal germ cell tumors revealed that the genomic alterations in CNS-GCTs are virtually indistinguishable from those found in their gonadal or other extragonadal counterparts of the corresponding age group. These data strongly argue in favor of common pathogenetic mechanisms in gonadal and extragonadal germ cell tumors. Keywords: germ cell tumor; central nervous system; extragonadal; chromosomal profile; isochromosome 12p; meta-analysis During childhood and adolescence, the majority of germ cell tumors arise outside of the gonads, and beyond early childhood, the central nervous system and the mediastinum constitute the most frequent sites of extragonadal germ cell tumors. 1 The vast majority of central nervous system germ cell tumors (CNS-GCTs) develop in the pineal gland or the suprasellar region, and approximately 10% of all CNS-GCTs present as bifocal tumors. 2,3 The extragonadal appearance of germ cell tumors is likely related to errors in germ cell migration during early embryonal development. Accordingly, imprinting studies of gonadal and extragonadal germ cell tumors show loss of the methylation imprint at imprinting control regions, correlating with the methylation status within early stages of primordial germ cell development. [4][5][6] However, the molecular mechanisms that interfere with normal homing of germ cells to the gonadal ridge and that allow for a

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Section: Discussionmentioning

confidence: 74%

Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization

et al. 2006

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“…ICGCTs have been associated with KS (Ahagon et al, 1983;Ellis et al, 1986;Arens et al, 1988;Prall et al, 1995;Wysocka et al, 1996). Here, we describe a molecular cytogenetic study on autopsy material and brain biopsies from 13 young males with ICGCTs.…”

Section: Discussionmentioning

confidence: 99%

Intracranial germ cell tumors: association with Klinefelter syndrome and sex chromosome aneuploidies

Queipo

Aguirre

Nieto

et al. 2008

Cytogenet Genome Res

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Intracranial germ cell tumors (ICGCTs) occur mainly in male children and adolescents. Polyploidy of the X chromosome and X hypomethylation have been suggested as mechanisms of malignant transformation independently of the histological tumor type. On the other hand, several reports associate these tumors with Klinefelter’s syndrome (KS). Recent reports indicate that KS patients have an increased relative risk for development of malignant mediastinal germ cell tumors and also around 8% of male patients with primary mediastinal tumors have KS. In an attempt to explore the frequency of KS amongst patients with ICGCTs and to confirm the presence of X chromosome polyploidies in these tumors, we studied 13 young male patients with ICGCTs. Paraffin-embedded tumoral and normal tissues were studied by FISH. KS was found in 15% of the cases, demonstrating that this constitutive aneuploidy may be related to carcinogenesis. When tumor and non-tumor tissues were compared, statistically significant X and Y chromosome polyploidies in tumors were revealed. These results emphasize that aneuploidies are involved in ICGCT tumorigenesis.

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“…Last, males with small, firm testes should undergo a chromosome study to evaluate for Klinefelter syndrome. They have an increased risk of extragonadal germ cell tumors (mediastinal and cerebral) and male breast cancer [Prall et al, 1995]. The breast cancer risk is similar to that of females and represents a 50-fold increase relative to normal males [Hultborn et al, 1997].…”

Section: Genital Tract Male Hypogonadismmentioning

confidence: 99%

Recognition and management of childhood cancer syndromes: A systems approach

Clericuzio

1999

Am. J. Med. Genet.

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Recognition of congenital anomalies that predispose to childhood cancer allows for the institution of a cancer surveillance program, identification of relatives with increased cancer risk, and recurrence risk counseling. In this article, a systems approach to the diagnosis of 21 childhood cancer syndromes is set forth in the format of the pediatric physical examination. In the second part of this article, guidelines are presented for genetic testing, cancer screening, and genetic counseling for the 21 cancer syndromes.

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Intracranial Malignant Germ Cell Tumor and the Klinefelter Syndrome

Cited by 25 publications

References 19 publications

Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization

Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization

Intracranial germ cell tumors: association with Klinefelter syndrome and sex chromosome aneuploidies

Recognition and management of childhood cancer syndromes: A systems approach

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