Global mapping of cancers: The Cancer Genome Atlas and beyond.

Cancer genomes have been explored from the early 2000s through massive exome sequencing efforts, leading to the publication of The Cancer Genome Atlas in 2013. Sequencing techniques have been developed alongside this project and have allowed scientists to bypass the limitation of costs for whole-genome sequencing (WGS) of single specimens by developing more accurate and extensive cancer sequencing projects, such as deep sequencing of whole genomes and transcriptomic analysis. The Pan-Cancer Analysis of Whole Genomes recently published WGS data from more than 2600 human cancers together with almost 1200 related transcriptomes. The application of WGS on a large database allowed, for the first time in history, a global analysis of features such as molecular signatures, large structural variations and noncoding regions of the genome, as well as the evaluation of RNA alterations in the absence of underlying DNA mutations. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine-learning approaches will be the next step towards the generation of personalized approaches for cancer medicine. The present manuscript wants to give a broad perspective on some of the biological evidence derived from the largest sequencing attempts on human cancers so far, discussing advantages and limitations of this approach and its power in the era of machine learning.

Serine and one-carbon metabolisms bring new therapeutic venues in prostate cancer.

Serine and one-carbon unit metabolisms are essential biochemical pathways implicated in fundamental cellular functions such as proliferation, biosynthesis of important anabolic precursors and in general for the availability of methyl groups. These two distinct but interacting pathways are now becoming crucial in cancer, the de novo cytosolic serine pathway and the mitochondrial one-carbon metabolism. Apart from their role in physiological conditions, such as epithelial proliferation, the serine metabolism alterations are associated to several highly neoplastic proliferative pathologies. Accordingly, prostate cancer shows a deep rearrangement of its metabolism, driven by the dependency from the androgenic stimulus. Several new experimental evidence describes the role of a few of the enzymes involved in the serine metabolism in prostate cancer pathogenesis. The aim of this study is to analyze gene and protein expression data publicly available from large cancer specimens dataset, in order to further dissect the potential role of the abovementioned metabolism in the complex reshaping of the anabolic environment in this kind of neoplasm. The data suggest a potential role as biomarkers as well as in cancer therapy for the genes (and enzymes) belonging to the one-carbon metabolism in the context of prostatic cancer.

Radioguided sentinel node biopsy to avoid unnecessary neck dissection in T1-T2N0 oral cavity squamous cell carcinoma: personal experience with same day protocol.

PURPOSE: Data from literature show a mean incidence of occult metastases of 33% in early OCSCC. The gold standard for most authors is a selective neck dissection and a routine pathological examination. 60-70% of unnecessary neck dissections with associated morbidity, can be avoided by using SNB. The aim of this study is to present the results of one of the major Italian centres for the SNB procedure, reserving neck dissection only for proven positive lymphatic metastases. METHODS: From July 2004 to March 2015, 48 patients with transorally resectable cT1-T2N0 oral SCC were submitted to a lymphoscintigraphic examination one-three hours before surgery and a radio-guided SNB (same day protocol). Patients with a negative SNB were checked every 3 months by ultrasound examination. The minimum follow-up was 5 years. RESULTS: Sentinel nodes were found in all cases, with 71% localized in the ipsilateral neck only in levels I-II. Metastases were found in 15 out of 48 cases (31.2%), on levels I, II and III. Further metastatic nodes were found in 6 cases in the neck dissection specimen. In the cohort of 33 patients with SNB negative at 5 years, no-one had a recurrence on the ipsilateral neck. CONCLUSION: This study confirms the accuracy of SNB in predicting the presence of occult metastases, sparing the need for unnecessary neck dissection in 70% of cases. The same day protocol is designed to detect sentinel nodes, which are almost always on neck level I-II, thereby limiting the number of nodes examined and the extension of the surgical approach.

Endometrial polyps and the risk of atypical hyperplasia on biopsies of unremarkable endometrium: a study on 694 patients with benign endometrial polyps.

The objective of our study was to examine the relationship between benign endometrial polyps and the underlying endometrium, analyzing factors associated with endometrial hyperplasia with and without atypia. Six hundred and ninety-four consecutive patients with benign endometrial polyps underwent hysteroscopic removal of the polyps combined with 2 biopsies of unremarkable endometrium. Hysteroscopic removal of endometrial polyps with 2 endometrial biopsies far from the base of the polyp were performed. The weight of each polyp was determined. Multivariable logistic regression analysis was used examining factors potentially associated with endometrial hyperplasia with and without atypia on endometrial biopsies. Overall, 18% of women had hyperplasia without atypia and 7.3% had atypia (with simple/complex hyperplasia) on hysteroscopically unremarkable endometrium. In postmenopause, 21.6% had hyperplasia without atypia, 12% atypia, and 1.2% adenocarcinoma on the sampled endometrium. At multivariable analysis, postmenopausal women with larger polyps had a 3.6-fold higher likelihood of atypia (odds ratio=3.6; 95% confidence interval: 1.3-10.3); in premenopause the likelihood of atypia was significantly associated with polyp weight and age above 40 years. Our findings suggest that important endometrial lesions are not always evident by hysteroscopic visualization. Therefore, endometrial biopsies should not be limited only to hysteroscopically evident lesions. Polypectomy should be combined with a histopathologic evaluation of the background endometrium, particularly in women with higher-risk characteristics.