Screening for Y microdeletions in men with testicular cancer and undescended testis

Bor, Pınar; Hindkjær, Johnny; Kølvraa, Steen; Rossen, Philip; Maase, Hans von der; Jørgensen, Troels Munch; Sørensen, Viggo Tønning; Eiberg, Hans; Ingerslev, Hans Jakob

doi:10.1007/s10815-005-9001-5

Cited by 12 publications

(15 citation statements)

References 14 publications

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“…Our study differs from previous studies in that we examined these regions in more detail by using a higher density of markers. Similar to the previous studies in Danish and Norwegian TGCT patients (Frydelund-Larsen et al, 2003;Lutke Holzik et al, 2005;Bor et al, 2006), no large contiguous deletions were demonstrated for any sample in this series in the AZF regions. We did not see the rate of noncontiguous deletions in the AZF regions demonstrated previously for Finnish patients and Argentinean TGCT patients (Bianchi et al, 2002(Bianchi et al, , 2006Richard et al, 2004), suggesting that there is either a difference in the rate of deletion between these populations or that there is some methodological issue giving rise to nonamplification of a PCR product rather that a true deletion of the Y chromosome DNA in these studies.…”

Section: Discussionsupporting

confidence: 91%

“…Several studies have examined constitutional DNA from TGCT patients for deletions of the AZF regions on the Y chromosome. A total of 457 TGCT patients were examined and no deletions were identified in the AZF regions (Frydelund-Larsen et al, 2003;Lutke Holzik et al, 2005;Bor et al, 2006). However, the STS markers used for the analysis would not detect the 'gr/gr' deletion.…”

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confidence: 99%

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A physical analysis of the Y chromosome shows no additional deletions, other than Gr/Gr, associated with testicular germ cell tumour

et al. 2007

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Testicular germ cell tumour (TGCT) is the most common malignancy in men aged 15 -45 years. A small deletion on the Y chromosome known as 'gr/gr' was shown to be associated with a two-fold increased risk of TGCT, increasing to three-fold in cases with a family history of TGCT. Additional deletions of the Y chromosome, known as AZFa, AZFb and AZFc, are described in patients with infertility; however, complete deletions of these regions have not been identified in TGCT patients. We screened the Y chromosome in a series of TGCT cases to evaluate if additional deletions of Y were implicated in TGCT susceptibility. Single copy Y chromosome STS markers with an average inter-marker spacing of 128 kb were examined in constitutional DNA of 271 index TGCT patients. Three markers showed evidence of deletions, sY1291, indicative of 'gr/gr' (eight out of 271; 2.9%), Y-DAZ3 contained within 'gr/gr' (21 out of 271; 7.7%) and a single deletion of the marker G66152 was identified in one TGCT case. No other markers demonstrated deletions. While several regions of the Y chromosome are known to be deleted and associated with infertility, our study provides no evidence to suggest regions of Y deletion, other than 'gr/gr', are associated with susceptibility to TGCT in UK patients. Testicular germ cell tumour (TGCT) is the most common cancer in men aged 15 -45 years. The worldwide incidence of the disease is 7.5 per 100 000, but the rates vary considerably between countries and racial and ethnic groups (Ferlay et al, 2004). The highest incidence of the disease occurs in men of European descent and the lowest in African and Asian groups (Ferlay et al, 2004). Risk factors for TGCT include a family history of disease (Forman et al, 1992;Heimdal et al, 1996;Westergaard et al, 1996;Sonneveld et al, 1999;Hemminki and Li, 2004), a previously diagnosed germ cell tumour (Osterlind et al, 1991; Wanderas et al, 1997), a history of undescended testis (UDT) (Brown et al, 1987;Swerdlow et al, 1997), infertility (Petersen et al, 1998;Moller and Skakkebaek, 1999;Jacobsen et al, 2001;Richiardi et al, 2004), atrophy (Harland et al, 1998) and gonadal dysgenesis (Verp and Simpson, 1987).Family history is one of the strongest of the underlying risk factors. Multiple studies have documented that brothers and fathers of patients with TGCT have a 8 -12-fold and 4 -6-fold risk, respectively (Forman et al, 1992;Heimdal et al, 1996;Westergaard et al, 1996;Sonneveld et al, 1999;Hemminki and Li, 2004). These relative risks are higher than for most other cancer types, which rarely exceed 4 (Hemminki et al, 2001) and suggest that there is a substantial contribution to the disease risk from underlying susceptibility genes.Despite the high familial risk, the underlying genetic susceptibility to the TGCT remains unclear. A recent genome-wide linkage search on 237 TGCT pedigrees, the largest series of TGCT families examined to date, identified several 'regions of interest' on chromosomes 2p33, 3p12, 3q26, 12q13 -q21, 18q21 -q23 and Xq27. Each region demonstrated a HLOD ...

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

A physical analysis of the Y chromosome shows no additional deletions, other than Gr/Gr, associated with testicular germ cell tumour

et al. 2007

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“…A few studies have focused on Υq11-md specifically in patients with TMD (Cortes et al, 1998;Fagerli et al, 1999;Foresta et al, 1999;Dada et al, 2002b;Suzuki et al, 2002;Kunej et al, 2003;Castro et al, 2004;Ferlin et al, 2004Ferlin et al, , 2005Song et al, 2005;Bor et al, 2006;Giachini et al, 2007;Moretti et al, 2007;Gurbuz et al, 2008). To our knowledge, our study is the largest one published to date (Table 1).…”

Section: Discussionmentioning

confidence: 76%

“…Similarly, another study including 42 adults with normal to severely impaired sperm concentrations and TMD yielded negative results (Fagerli et al, 1999). Similarly, in a study of 64 Danish patients with TMD and abnormal or normal semen analysis, no Yq11-md were detected leading the authors to conclude against an association (Bor et al, 2006). Furthermore, in a small study of 10 selected patients with TMD as a clinical characteristic of Prader-Willi syndrome, Suzuki et al (2002) investigated the possibility that Yq11-md might be associated with the TMD observed in this specific subgroup of patients.…”

Section: Discussionmentioning

confidence: 96%

Screening for Y chromosome microdeletions in childhood: lack of evidence for a direct association with testicular maldescent

et al. 2012

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The aim of the study was to investigate the hypothesis that Y chromosome microdeletions are directly implicated in testicular maldescent. Genomic DNA was extracted from the peripheral blood of 292 subjects. This population consisted of (i) 180 children with all phenotypes of isolated (non-syndromic) testicular maldescent from 174 index families, (ii) affected adult relatives available (n = 12) and (iii) 100 unrelated children with normal external genitalia (controls). The sequence-tagged site primer set and the conditions of conventional polymerase chain reaction amplification were based on the current laboratory guidelines for molecular diagnosis of Y chromosome microdeletions recommended by the European Academy of Andrology and the European Molecular Genetics Quality Network. Two multiplex reactions were designed to screen the regions of azoospermic factors a, b and c. Each multiplex reaction included adequate internal and external amplification controls. Amplification products were submitted to electrophoresis on 2% agarose gel impregnated with ethidium bromide dye solution for 80 volt-h and visualised under ultraviolet light. No microdeletions were detected in any subject. These results indicate that Y chromosome microdeletions are not directly implicated in the pathogenesis of testicular maldescent. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.

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“…That indeed c-KIT has an important role in the pathogenesis of TGCTs, is supported by deletions (removing all STSs located in a given AZF region) are not associated with TGCT and were not found at all in a total of 575 cancer patients. 37,[39][40][41] Single STS deletions on the Y chromosome are likely to be due to PCR artefacts or to polymorphisms in the primer sequence binding site 41,42 which implies that they must be confirmed by sequencing the deletion breakpoints. Since confirmed single STS deletions have not been described in the literature the appealing link between Y chromosome instability (expressed as mosaic or single STS deletions) and TGCT remains to be established.…”

Section: The Role Of Somatic Genetic Changesmentioning

confidence: 99%

Genetic aspects of testicular germ cell tumors

Krausz

Looijenga²

2008

Cell Cycle

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Testicular Germ Cell Tumor (TGCT) is the most common malignant tumor in young Caucasian men with an annual increase of 3-6% in the past 50 years. Data in the literature indicate that both environmental and genetic factors acting on the primordial gonocyte/gonocyte are implicated in the etiopathogenesis of this tumour. Genetic linkage and genome-wide analyses did not reveal a major gene effect so far, implying that multiple loci must contribute to the development of TGCTs. Only one significant genetic risk factor has been reported, the so called "gr/gr" deletion of the Y chromosome which still request further confirmation by independent studies. On the other side, the analysis of somatic genetic changes through mutation and genome imbalance analyses and expression profiling has just began to unravel the complex interaction of multiple pathways involved in TGCTs. This review focuses on genetic factors (both genomic and somatic) involved in the etiology, progression and treatment sensitivity of TGCTs.

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Screening for Y microdeletions in men with testicular cancer and undescended testis

Cited by 12 publications

References 14 publications

A physical analysis of the Y chromosome shows no additional deletions, other than Gr/Gr, associated with testicular germ cell tumour

A physical analysis of the Y chromosome shows no additional deletions, other than Gr/Gr, associated with testicular germ cell tumour

Screening for Y chromosome microdeletions in childhood: lack of evidence for a direct association with testicular maldescent

Genetic aspects of testicular germ cell tumors

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