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DNA double-strand breaks are the most critical DNA damage to cells, and their repair is tightly regulated to maintain cellular integrity. Some cancers exhibit homologous recombination deficiency (HRD), a faithful double-strand break repair system, making them more sensitive to poly (ADP ribose) polymerase inhibitors (PARPi). PARPi have shown substantial efficacy in BRCA-mutated ovarian cancer for several years, and their indication has gradually been extended to other tumour locations such as breast, prostate and pancreas. More recently, PARPi were demonstrated to be effective in cancers with an HRD phenotype beyond BRCA mutations. Today, a major challenge is developing tests capable of detecting the HRD phenotype of cancers (HRD tests) and predicting sensitivity to PARPi to select patients likely to benefit from this therapy. This review provides a synthesis of the existing HRD tests, divided into three main approaches to detect HRD: the investigation of the HRD causes, the study of its consequences and the evaluation of the HR activity itself.

We report the case of a hobnail variant of papillary thyroid carcinoma revealed by a cervical mass in a 67 years-old patient. This new entity in the 2017 WHO classification is rare. Histopathological diagnosis is based on four main criteria, present in≥30% of tumor cells: a discohesive tumor, micropapillary structures and loss of cell polarity and hobnail cells. This tumor expresses markers of thyroid differentiation. The most widely described molecular alteration is BRAF V600E mutation associated with other alterations, especially p53 mutations. This reflects the agressivness of this variant. It is important to recognize the hobnail variant of papillary thyroid carcinoma and to specify it in the pathological report because of its more pejorative prognosis, with local invasion, lymph node and distant metastasis, and deacreased survival. No specific management is recommended, but a close follow up seems necessary.

International audience; Objective: Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamide, Vincristine) and EMA-EP(Etoposide, Cisplatine)] regimens.Methods: We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma.Results: We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p < 0.05). In polychemoresistant choriocarcinoma (n = 20) we did not identify differentially expressed genes with an FDR adjusted p-value ≤ 0.05 when compared to polychemosensitive choriocarcinoma (n = 15). Gene pathway analysis revealed a predicted activation of IFN ᵞ in monochemoresistant choriocarcinoma and inhibited IL2 and TNF in polychemoresistant choriocarcinoma. The main biological functions predicted to be altered in chemoresistant choriocarcinoma were related to immunological homeostasis and leukopoiesis.Conclusion: HLA-G is a strong candidate gene to predict choriocarcinoma resistance to monochemotherapy and that further studies are required to implement its routine quantification in the decision process for the management of gestational choriocarcinoma.

We report the case of an 11-year-old patient diagnosed with a solid variant of papillary thyroid carcinoma. Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, representing 80-90% of all newly diagnosed thyroid cancers. Among the many variants described, solid/trabecular variant of papillary thyroid carcinoma is a rare entity and account for 3% of thyroid cancers. It is more common in children and young adults, and it is seen in higher proportion in post radiation papillary thyroid carcinoma cases. Histologically, solid variant papillary carcinoma is characterized by a predominantly solid, trabecular or insular growth pattern, and the presence of cytological features typical of PTC. Its main differential diagnosis is poorly differentiated thyroid carcinoma. It has a less favorable prognosis than the classical papillary type, with a higher risk of distant metastasis, extrathyroidal extension and lympho-vascular invasion. It is associated with a slightly lower long-term survival in adult cases, but not in children. The management of solid variant PTC includes surgery, associated or not with postoperative radioiodine ablation, according to the aggressiveness criteria. Our patient had a DICER1 somatic mutation. Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome, with a higher risk of numerous tumors and infrequently differentiated thyroid carcinomas.

Let R be a commutative ring that is free of rank k as an abelian group, p a prime, and S L n ( R ) the special linear group. We show that the Lie algebra associated to the filtration of S L n ( R ) by p -congruence subgroups is isomorphic to the tensor product s l n ( R ⊗ Z Z / p ) ⊗ F p t F p [ t ] , the Lie algebra of polynomials with zero constant term and coefficients n × n traceless matrices with entries polynomials in k variables over F p . We also use the underlying group structure to obtain several homological results. For example, we compute the first homology group of the level p -congruence subgroup for n ≥ 3 . We show that the cohomology groups of the level p r -congruence subgroup are not finitely generated for n = 2 and R = Z [ t ] . Finally, we show that for n = 2 and R = Z [ i ] (the Gaussian integers) the second cohomology group of the level p r -congruence subgroup has dimension at least two as an F p -vector space.

Testosterone (T) circulates in the blood tightly bound to sex hormone-binding globulin (SHBG) and weakly to albumin. Measuring protein unbound T (free) or non-SHBG-bound T rather than total T has been recommended for the evaluation of androgen disorders in humans. Ammonium sulfate precipitation has been widely used to separate [SHBG-T] complex from free and albumin-bound T. To achieve more specificity in this separation, we used monoclonal anti-SHBG antibody and developed a suitable and convenient immunoassay for measuring non-SHBG-bound T. Magnetic beads were covalently coupled to a monoclonal anti-SHBG antibody to capture [SHBG-T] complex from plasma samples. Magnetic separation was then performed to allow measurement of non-SHBG-bound T in the supernatant by direct radioimmunoassay. When 300 microL of plasma samples were incubated at room temperature with 10 microL of anti-SHBG beads, residual SHBG concentration was undetectable in the supernatant. The specificity of proteins retained on anti-SHBG beads was further demonstrated by peptide mass fingerprint on a MALDI-TOF analyzer. The non-specific adsorption of T on beads was low (5%), and dissociation of T from SHBG-T complex was less than 5% after 180 min of incubation. The plasma concentrations of non-SHBG-bound T using anti-SHBG beads were highly correlated to those obtained using ammonium sulfate precipitation. We conclude that SHBG immunocapture is a highly specific and useful tool for an experimental direct measurement of plasma non-SHBG-bound T. This methodology is also convenient and appropriate for routine and automated assay.

Fine needle aspiration (FNA) is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. Recently use of molecular biomarkers was proposed to improve pathologic accuracy. We evaluated feasibility and performance of molecular analysis in liquid-based FNA (LB-FNA) with indeterminate cytology. Mutation profiling of NRAS, HRAS and BRAF was performed on residual material from LB-FNA of 215 cases including 83 atypia of undetermined significance (AUS), 72 follicular neoplasms (FN), 46 suspicious for malignancy (SM), and 14 malignant (M). Forty-eight (22%) cases were mutated. Twenty-four cases presented a RAS mutation (19 NRAS and 5 HRAS) (11 AUS, 6 FN, and 7 SM) and 24 were carrying a BRAF mutation (1FN, 11 SM, and 12M). Surgical samples were available for 38 cases: 3 AUS, 14 FN, 13 SM and 8M. In the AUS category, 1 was a papillary carcinoma (PC) with NRAS mutation and 2 were benign (1 with NRAS mutation). In the FN category, 3 were malignant (1 with BRAF and 1 with HRAS mutation) and 11 benign (1 with HRAS and 1 with NRAS mutation). In the SM group, 10 were PC (3 with NRAS mutation and 5 with BRAF mutation) and 3 benign (no mutation). In the M group, all were PC with BRAF mutation. In conclusion, mutation profiling of BRAF and RAS can be successfully performed on residual material of thyroid LB-FNA and could improve the diagnostic accuracy of FNA.