Over the past 10 years, circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) have received enormous attention as new biomarkers and subjects of translational research. Although both biomarkers are already used in numerous clinical trials, their clinical utility is still under investigation with promising first results. Clinical applications include early cancer detection, improved cancer staging, early detection of relapse, real-time monitoring of therapeutic efficacy, and detection of therapeutic targets and resistance mechanisms. Here, we propose a conceptual framework of CTC and ctDNA assays and point out current challenges of CTC and ctDNA research, which might structure this dynamic field of translational cancer research. SIGNIFICANCE: The analysis of blood for CTCs or cell-free nucleic acids called "liquid biopsy" has opened new avenues for cancer diagnostics, including early detection of tumors, improved risk assessment and staging, as well as early detection of relapse and monitoring of tumor evolution in the context of cancer therapies.

Liquid Biopsy: From Discovery to Clinical Application.

Name Sequence Exon 2 mG6pc S 5’-TCCCTGTCACCTGTGAG-3’ Exon 5 mG6pc AS 5’-CACAAGAAGTCTTTGTAA-3’ Exon1 mG6pcS 5’-TTACCAAGACTCCCAGGACTG-3’ Exon2 mG6pcAS 5’-GAGCTGTTGCTGTAGTAGTCG-3’ Pck1S 5’-AGCCTTTGGTCAACAACTGG-3’ Pck1AS 5’-TGCCTTCGGGGTTAGTTATG-3’ GcgR S 5’-ACCCAACTATTGCTGGTTGC-3’ GcgR AS 5’-CCATGTTGTCATTGCTGGTC-3’ Hmgcs2 S 5’-CCGTATGGGCTTCTGTTCAG-3’ Hmgcs2 AS 5’-AGCTTTGTGCGTTCCATCAG-3’ mL19S 5’-AGAAGATTGACCGCCATAT-3’ mL19AS 5’-TTCGTGCTTCCTTGGTCTTAGA-3’ CRU G6pc S 5’-TTTGCTATTTTACGTAAATCACCCT-3’  CRU G6pc AS 5’-GTACCTCAGGAAGCTGCCA-3’ CRU Pck1 S 5’-GGCCTCCCAACATTCATTAAC-3’ CRU Pck1 AS 5’-GTAGCTAGCCCTCCTCGCTTTAA-3’ GRU G6pc S 5’-CACCCCTTAGCACTGTAAGCCGTGTG-3’ GRU G6pc AS 5’-GGATTCAGTCTGTAGGTCAACCTAGCCC-3’ GRU Pck1 S 5’-TGCAGCCAGCAACATATGAA-3’

Supplementary table 1

ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up

Clinical applications of the CellSearch platform in cancer patients.

Testicular germ cell tumours (TGCTs) are the most common cancer in young men. Here we perform whole-exome sequencing (WES) of 42 TGCTs to comprehensively study the cancer's mutational profile. The mutation rate is uniformly low in all of the tumours (mean 0.5 mutations per Mb) as compared with common cancers, consistent with the embryological origin of TGCT. In addition to expected copy number gain of chromosome 12p and mutation of KIT, we identify recurrent mutations in the tumour suppressor gene CDC27 (11.9%). Copy number analysis reveals recurring amplification of the spermatocyte development gene FSIP2 (15.3%) and a 0.4 Mb region at Xq28 (15.3%). Two treatment-refractory patients are shown to harbour XRCC2 mutations, a gene strongly implicated in defining cisplatin resistance. Our findings provide further insights into genes involved in the development and progression of TGCT.

/pdf/whole-exome-sequencing-reveals-the-mutational-spectrum-of-3cd8zryhg5.pdf

Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours

Objectives Testicular germ cell tumors (GCTs) have their incidence peak in the third and fourth decades of life. Histologically, GCTs comprise of seminoma and nonseminoma at almost equal proportions with a slight preponderance of nonseminoma in most of the major series. Since decades, there is a shift toward decreasing age at presentation. Recently, there are suggestions of a reversal of the age trend, and also, the histologic subtype ratio appears to shift toward seminoma. We retrospectively looked to our patient populations to verify these recent trends. Methods A total of 2,482 patients with histologically proven GCT diagnosed between 1976 and 2010 were retrospectively evaluated regarding the year of diagnosis, histology of primary tumor, and age at presentation. Patients were categorized according to the following time periods of treatment: before 1990, 1990 to 1994, 1995 to 1999, 2000 to 2004, and 2005 to 2010. Mean age and relative proportion of seminoma were compared among patient categories by employing the chi-square test and analysis of variance, respectively. Results The mean age significantly increased from 28 to 36 years. The age difference between the 2 histologic subtypes remained constant between 6 and 8 years during the entire observation period. The relative proportion of seminoma continuously increased from 30.9% to 56% (P Conclusion There is evidence of a significant shift toward older age at diagnosis of GCT. In addition, the proportion of seminoma is constantly increasing at the expense of nonseminoma. The reasons for these developments are obscure. However, 2 old theories regarding the pathogenesis of GCT may receive support from our results: first, the theory of divergent pathogenetic pathways of seminoma and nonseminoma and second, the involvement of postnatal environmental factors in the pathogenesis of GCTs.

Changes in epidemiologic features of testicular germ cell cancer: Age at diagnosis and relative frequency of seminoma are constantly and significantly increasing

The Search for Biomarkers of Metastatic Seminoma

703 circulating tumor cells can be detected in patients with testicular germ cell tumors

Purpose
To examine the significance of 90 biomarkers for predicting metastatic status in non-seminomatous germ cell tumors (NSGCT). By predicting metastatic status, it may be possible to eliminate unnecessary therapeutic or diagnostic efforts.

Prediction of metastatic status in non-seminomatous testicular cancer.

Objectives. Environmental factors expose an individual to heavy metals that may stimulate cancer growth preclinically including non-small cell lung cancer (NSCLC) cells. Here, we examine the prevalence of four heavy metals present in postsurgical tissues from individuals with and without NSCLC. Materials and Methods. Thoracic tissue samples from two separate sample sets were analyzed for cadmium (Cd), arsenic (As), mercury (Hg), and lead (Pb) content. Results. In the first sample set, there was no significant measurable amount of Pb and Hg found in either NSCLC tissue or nonmalignant lung tissue samples. Cd was the most prevalent heavy metal and As was present in moderate amounts. In the second sample set, Cd was measurable across all tissue types taken from 28 NSCLC patients and significantly higher Cd was measurable in noncancer benign lung (n = 9). In the NSCLC samples, As was measurable in moderate amounts, while Hg and Pb amounts were negligible. Conclusion. Cd and As are present in lung tissues for patients with NSCLC. With existing preclinical evidence of their tumorigenecity, it is plausible that Cd and/or As may have an impact on NSCLC development. Additional studies examining the prevalence and association between smokers and nonsmokers are suggested.

/pdf/heavy-metal-content-in-thoracic-tissue-samples-from-patients-3slp5kc07n.pdf

Heavy Metal Content in Thoracic Tissue Samples from Patients with and without NSCLC

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