Identifying novel circulating biomarkers predictive of response and informative about the mechanisms of resistance, is the new challenge for breast cancer (BC) management. The integration of omics information will gradually revolutionize the clinical approach. Liquid biopsy is being incorporated into the diagnostic and decision-making process for the treatment of BC, in particular with the analysis of circulating tumor DNA, although with some relevant limitations, including costs. Circulating cell-free DNA (cfDNA) fragmentomics and its integrity index may become a cheaper, noninvasive biomarker that could provide significant additional information for monitoring response to systemic treatments in BC. The purpose of our review is to focus on the available research on cfDNA integrity and its features as a biomarker of diagnosis, prognosis and response to treatments in BC, highlighting new perspectives and critical issues for future applications.

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Mediastinal germ cell tumors (MGCTs) share histologic, molecular and biomarkers features with testicular GCTs; however, nonseminomatous MGCTs are usually more aggressive and have poorer prognosis than nonseminomatous TGCTs. Most nonseminomatous MGCT cases show early resistance to platinum-based therapies and seldom have been associated with the onset of one or more concomitant somatic malignancies, in particular myeloid neoplasms with recent findings supporting a common, shared genetic precursor with the primary MGCT. Genomic, transcriptomic and epigenetic features of testicular GCTs have been extensively studied, allowing for the understanding of GCT development and transformation of seminomatous and nonseminomatous histologies. However, MGCTs are still lacking proper multi-omics analysis and only few data are reported in the literature. Understanding of the mechanism involved in the development, in the progression and in their higher resistance to common therapies is still poorly understood. With this review, we aim to collect all molecular findings reported in this rare disease, resuming the similarities and disparities with the gonadal counterparts.