Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis

Spiller, Cassy M.; Bowles, Josephine

doi:10.1016/j.biocel.2017.03.004

Cited by 22 publications

(23 citation statements)

References 34 publications

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“…The reason for this contrast may partly be due to the localization of the tumor within the testis. Typically, the developed GCNIS is found above the basement membrane in seminiferous tubules, which are located in the intratesticular environment and therefore separate from the bloodstream via the blood testis barrier (BTB) (49,50). The BTB's primary function is to prevent both antibodies and T lymphocytes from affecting the testis (51).…”

Section: Discussionmentioning

confidence: 99%

Serum RNA Profiling in the 10-Years Period Prior to Diagnosis of Testicular Germ Cell Tumor

et al. 2020

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Although testicular germ cell tumor (TGCT) overall is highly curable, patients may experience late effects after treatment. An increased understanding of the mechanisms behind the development of TGCT may pave the way for better outcome for patients. To elucidate molecular changes prior to TGCT diagnosis we sequenced small RNAs in serum from 69 patients who were later diagnosed with TGCT and 111 matched controls. The deep RNA profiles, with on average 18 million sequences per sample, comprised of nine classes of RNA, including microRNA. We found that circulating RNA signals differed significantly between cases and controls regardless of time to diagnosis. Different levels of TSIX related to X-chromosome inactivation and TEX101 involved in spermatozoa production are among the interesting findings. The RNA signals differed between seminoma and non-seminoma TGCT subtypes, with seminoma cases showing lower levels of RNAs and non-seminoma cases showing higher levels of RNAs, compared with controls. The differentially expressed RNAs were typically associated with cancer related pathways. Our results indicate that circulating RNA profiles change during TGCT development according to histology and may be useful for early detection of this tumor type.

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Section: Discussionmentioning

confidence: 99%

Serum RNA Profiling in the 10-Years Period Prior to Diagnosis of Testicular Germ Cell Tumor

et al. 2020

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“…These are usually manifested by antenatal origin. Undescended testis and hypospadias give symptoms at neonatal period whereas poor quality of semen and development of TGCT manifest after puberty (9). Animal models and epidemiological researches have revealed that deficiencies in the production of androgens, disorders of androgen receptor expression, disturbance in androgen levels, exposure to anti-androgenic or estrogenic disruptors were attributed to the pathogenesis of TDS (6,15).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, more evidence is needed to reinforce TDS hypothesis (8). According to the literature, semen analysis and testicular histology support the association between TGCT and TDS (9). But there is no detailed evaluation to show the effects of TDS components on TGCT prognosis.…”

Section: Introductionmentioning

confidence: 99%

Effects of testicular dysgenesis syndrome components on testicular germ cell tumor prognosis and oncological outcomes

et al. 2020

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Purpose: To evaluate whether components of Testicular Dysgenesis Syndrome (TDS) affect testicular germ cell tumor (TGCT) prognosis and oncological outcomes. According to the hypothesis called TDS; undescended testis, hypospadias, testicular cancer and spermatogenic disorders share the same risk factors and have a combined fetal origin. Materials and Methods: We retrospectively evaluated the stages and oncological outcomes of 69 patients who underwent radical orchiectomy between January 2010 and December 2014 due to TGCT in our department. The presence of undescended testis, hypospadias and semen parameters disorders were recorded according to anamnesis of patients. Results: Among 69 patients with TGCT, only 16 (23.1%) had TDS. Significantly higher rate of TDS (36.1% vs. 9.1%) was observed at the advanced stages of TGCT(p=0.008). In the TDS group, the rates of local recurrence (50% vs. 11.3%, p<0.001), distant metastasis (93.6% vs. 3.8%, p<0.001) and cancer-spesific mortality (87.5% vs. 3.8%, p<0.001) were found significantly higher than those without TDS. The predicted time for recurrence-free survival (13.70±5.13 vs. 100.96±2.83 months, p<0.001) metastasis-free survival (13.12±4.21 vs. 102.79±2.21 months, p <0.001) and cancer-specific survival (13.68±5.38 vs. 102.80±2.19 months, p<0.001) were also statistically lower in this group. Conclusions: According to our preliminary results, there is an apparent relationship between TDS and tumor prognosis. Even if the components of TDS alone did not contain poor prognostic features for TGCT, the presence of TDS was found as the most important independent predictive factor for oncological outcomes in both seminomas and nonseminomas as well as all patients with TGCT.

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“…These cancers are clinically and histologically classified into two variants, being seminoma (SE) and nonseminoma (NS). Both arise from a common cancer stem cell, currently referred to as Germ Cell Neoplasia In Situ (GCNIS) 2,3 , which resembles totipotent primordial germ cells (PGC) / gonocytes. Patients with proven GCNIS have a 70% chance of progression to TGCC (both SE and NS) within 7 years.…”

Section: Introductionmentioning

confidence: 99%

“…About 50% of the TGCC patients present with a NS, that can be composed of different histological elements, embryonal carcinoma (EC), teratoma (TE), yolk sac tumor (YST), and choriocarcinoma (ChC), either pure or mixed. The EC is the pluripotent stem cell component of NS, which can mimic normal early embryogenesis including the formation of so called embryonal bodies (EB), and thereby give rise to all differentiated components [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

Molecular Heterogeneity and Early Metastatic Clone Selection in Testicular Germ Cell Cancer Development

Dorssers

Gillis

Stoop

et al. 2018

Preprint

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Novelty and Impact: The nonseminoma subtype of testicular germ cell cancer is characterized by totipotency of the cancer stem cell which may differentiate into all embryonal tissue lineages.We investigated a large series of purified tumor cell samples of four nonseminoma cases using different omics methods. We demonstrate that intratumoral heterogeneity exists among the cancer stem cells and the histological components. Furthermore, metastases appeared to be derived from cancer stem cells not identified in the primary tumor.Keywords (3-5): Tumor Initiation; Genome Duplication; Copy Number Alteration; Cancer Progression, Cancer Stem Cell Abbreviations used: CG: Complete Genomics Inc.; ChC: choriocarcinoma; CNA: copy number alterations; dAP: direct alkaline phosphatase; EB: embryonal bodies; EC: embryonal carcinoma; FISH: fluorescent in situ hybridization; GCNIS: germ cell neoplasia in situ; IHC: immunohistochemistry; LAF: lesser allele frequency; LOH: loss of heterozygosity; NAP: nonmalignant adjacent parenchyma; NS: nonseminoma ; PGC: primordial germ cells; SE: seminoma; SNP: single nucleotide polymorphism; SNV: somatic DNA variants; TE: teratoma; TGCC: testicular germ cell cancer; TGCT: testicular germ cell tumor; WGS: whole genome sequencing; YST: yolk sac tumor.All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/385807 doi: bioRxiv preprint first posted online Aug. 8, 2018; 3 Abstract Testicular germ cell cancer (TGCC) is initiated during early life from a totipotent embryonic germ cell, and the most frequent malignant cancer in young Caucasian males. The goal of this study is to determine the intratumor heterogeneity, and to unravel tumor progression from initiation till therapy-resistant metastasis. In this study, we have investigated 42 purified samples of four cases of nonseminoma with intrinsic resistance to chemotherapy including different histological elements, metastatic specimens and the precursor cancer stem cells (germ cell neoplasia in situ, GCNIS) using whole genome-, and targeted sequencing. Sequence data were used to reconstruct the evolution of these cancers. Intratumor molecular heterogeneity was observed and did not correspond to the supposed histological evolution of the primary tumor. Metastases after systemic treatment were derived from cancer stem cells frequently not identified in the primary cancer. The GCNIS mostly lacked the molecular marks of the primary TGCC and comprised dominant clones that had failed to progress into a manifest malignancy. A BRCA-like mutational signature was found without evidence for direct involvement of BRCA1 and BRCA2

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Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis

Cited by 22 publications

References 34 publications

Serum RNA Profiling in the 10-Years Period Prior to Diagnosis of Testicular Germ Cell Tumor

Serum RNA Profiling in the 10-Years Period Prior to Diagnosis of Testicular Germ Cell Tumor

Effects of testicular dysgenesis syndrome components on testicular germ cell tumor prognosis and oncological outcomes

Molecular Heterogeneity and Early Metastatic Clone Selection in Testicular Germ Cell Cancer Development

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