Rapid technical advances in molecular biology allowed for the identification of key genetic alterations in central nervous system (CNS) tumors. Our ever-expanding knowledge of brain tumor genetics and the development of new technologies, such as DNA-methylation profiling, required an update of the 2016 fourth edition of the WHO classification of CNS tumors. Updates were regularly published by the Consortium to Inform Molecular Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (c-IMPACT-NOW) until the publication of the fifth edition of the WHO classification of CNS tumors in 2021. In that edition, new types and subtypes are introduced and criteria for histo-molecular diagnostic and grading are refined, especially for diffuse gliomas. The definition of a broad category "diffuse glioma, pediatric subtype" (low or high grade) is a major improvement of the classification. Moreover, the nomenclature was simplified and aligned with that of other blue books. The 2021 edition truly advances the role of molecular diagnostics in CNS tumor classification. Methyloma profiling may become a cornerstone of CNS tumor diagnostic. The new WHO classification will lead to better management of brain tumor patients.

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.

PARP inhibitors are effective in different types of tumors such as ovarian, breast, prostate and pancreatic cancer. Many studies are in progress and may lead to prescription evolution. PARP inhibitors prescription is almost reserved to patients with a constitutional BRCA mutation or a somatic BRCA alteration or a tumor with a deficiency in homologous recombination. Nowadays, the diagnosis of homologous recombination deficit, HRD, is possible with the prescription of a myChoice CDx (Myriad) test. PARP inhibitors are studied in association with chemotherapy and targeted therapies but also with radiotherapy and with immune checkpoint inhibitors. Access to PARP inhibitors is challenged with the emergence of resistance mechanism. Various trials are now studying the possibility of reversing these resistance mechanisms.

Refractory thyroid cancers include radio-iodine-refractory cancers, metastatic or locally advanced unresectable medullary and anaplastic thyroid cancers. Their management has been based for several years on the use of multi-target kinase inhibitors, with anti-angiogenic action, with the exception of anaplastic cancers usually treated with chemo- and radiotherapy. The situation has recently evolved due to the availability of molecular genotyping techniques allowing the discovery of rare but targetable molecular abnormalities. New treatment options have become available, more effective and less toxic than the previously available multi-target kinase inhibitors. The management of refractory thyroid cancers is therefore becoming more complex both at a diagnosis level with the need to know when, how and why to look for these molecular abnormalities but also at a therapeutic level, innovative treatments being hardly accessible. The cost of molecular analyzes and the access to treatments need also to be homogenized because disparities could lead to inequality of care at a national or international level. Finally, the strategy of identifying molecular alterations and treating these rare tumors reinforces the importance of a discussion in a multidisciplinary consultation meeting.

The presence of multiple synchronous lung tumors is not a rare event. Distinguishing intra-pulmonary metastases from multiple synchronous lung adenocarcinoma is a challenge for pathologists and physicians. We present observation of a patient with three lung tumors corresponding to three adenocarcinomas for which molecular analysis had a significant impact on tumor staging.

We are taking advantage of the launch of the latest version (v4.6) of our web-based data mining tool "breast cancer gene-expression miner" (bc-GenExMiner) to take stock of its position within the oncology research landscape and to present an activity report ten years after its establishment (http://bcgenex.ico.unicancer.fr). bc-GenExMiner is an open-access, user-friendly tool for statistical mining on breast tumor transcriptomes, annotated with more than 20 clinicopathologic and molecular characteristics. The database comprises more than 16,000 patients from 64 cohorts - including TCGA, METABRIC and SCAN-B - for whom several thousands of genes have been quantified by microarrays or RNA-seq. Correlation, expression and prognostic analyses are available for targeted, exhaustive or customized explorations of queried genes. bc-GenExMiner facilitates the validation, investigation, and prioritization of discoveries and hypotheses on genes of interest. It allows users to analyse large databases, create data visualizations, and obtain robust statistical analysis, thereby accelerating biomarker discovery. Ten years after its launch, judging by the number of visits, analyses, and scientific citations of bc-GenExMiner, we conclude that this web resource serves its purpose in the international scientific community working in breast cancer research, with a never-ending rise in its use.

Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers.

The last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology.

Numerous clinical studies aim to integrate immunotherapy in radiotherapy oncology, either for generating abscopal responses in metastatic patients in combination with radiotherapy, or in the treatment of a locally advanced tumor. The search for biomarkers of response to treatment is a major axis in the development of these therapeutic combinations, to allow the early identification of patients who will benefit from the treatment, in the context of an increasingly personalized approach. We review some of the strategies that can be applied for personalization to combined radiotherapy and immunotherapy treatments.

The treatment of endometrial carcinomas relies on histopathological data such as tumor type, grade, stage, and lymphovascular invasion. We herein present the recent advances in the pathological appreciation of these criteria, relying in the last 2020 WHO classification of female genital tumours. Furthermore, molecular typing of endometrial carcinoma has become a rule with strong prognostic and therapeutic implications. The TP53-mutated/serous-like and hypermutated/dMMR groups can be easily identified by the pathologist using immunohistochemistry. The ultramutated/POLE-mutated group identification requires sequencing technologies. We herein explain how easily incorporate this novel histomolecular classification, now included in scholarly society recommendations, in the pathologist routine.

Meningiomas are the most frequent among intracranial tumors, and represent more than 30% of primitive central nervous system neoplasms. Arising from the meninges, they are generally benign lesions and can be treated by either radio-clinical follow-up or surgical resection with excellent outcome. However, more than 20% of meningiomas harbor atypical or malignant features and represent challenges for both prognostic evaluation and therapeutic strategy. The discovery of the genetic and epigenetic landscapes of meningiomas enabled the identification of new prognostic markers and potential therapeutic targets for refractory meningiomas. This review summarizes current epidemiology, histological and molecular characteristics, diagnosis and treatments for meningiomas, and highlights the close relationship between the development of meningiomas and hormonal intake, as illustrated by recent recommendations of the "Agence Nationale de Securité du Medicament", the French national drug safety agency.

Colorectal cancer (CRC) is a major global public health problem. Folate metabolism is involved in DNA synthesis, repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Common MTHFR C677T polymorphism was correlated to CRC. This case-control study was conducted to analyze the association between this polymorphism and the risk of sporadic CRC in a Moroccan population. The study involved 76 patients with sporadic colorectal cancer confirmed histologically and 182 patients (control group) without a history of cancer. Deoxyribonucleic acid (DNA) was isolated from peripheral blood and genotypes were determined using PCR-RFLP. The risk of association was estimated using odds ratio (OR) with 95% confidence interval. Genotype frequency of MTHFR in patients and in the control group was CC 34.1%, CT 56.6%, TT 9.21%, CC 51.6%, CT 42.8% and TT 6% respectively. CT genotype and its combination with TT genotype and allele T were associated with an increased risk of CRC and with an OR of 2.02 (with 95% confidence interval [CI]: 1.14-3.58, p = 0.01), 2.05 (95 % CI: 1.18-3.58, p= 0.01) and 1.61 (95% CI: 1.07-2.40, p=0.02). Homozygous TT weren´t a protection factor in our study, with an OR of 2.30 (95% CI: 0.81-6.52, p = 0.11). There was a statistically significant association between the MTHFR C677T variant and the risk of occurrence of sporadic colorectal cancer in the studied population.

The majority of non-small cell lung cancers are diagnosed as advanced disease. Subsets of adenocarcinomas and of squamous cell carcinomas in nonsmokers present a molecular aberration leading to tumour survival. Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) and Repressor Of Silencing1 (ROS1) have been identified and targeted with good efficacy for fifteen years. Newer inhibitors brought even greater efficacy with a generally better tolerability. Other molecular aberrations (Kirsten Rat Sarcoma, Rearranged during Transfection, MET, NeuroTrophic Receptor yrosine kinase) are targets for newly developed, more selective drugs. As more and more patients will benefit from targeted therapies, the identification of molecular aberration is more than ever crucial for optimal lung cancer patient care.