Double minute chromosomes harboring MDM2 amplification in a pediatric atypical lipomatous tumor

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BRCA1/2 Pathogenic Variants Are Not Common in Merkel Cell Carcinoma: Comprehensive Molecular Study of 30 Cases and Meta-Analysis of the Literature

International audienceMerkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer. Management of advanced MCC is mainly based on immune-checkpoint inhibitors. The high failure rate warrants an investigation of new therapeutic targets. The recent identification of BRCA1 or BRCA2 (BRCA1/2) mutations in some MCC raises the issue of the use of poly-(ADP-Ribose)-polymerase inhibitors in selected advanced cases. The main objective of our study is to determine the accurate frequency of BRCA1/2 pathogenic variants. We studied a series of 30 MCC and performed a meta-analysis of BRCA1/2 variants of published cases in the literature. In our series, we detected only one BRCA2 pathogenic variant. The low frequency of BRCA1/2 pathogenic variants in our series of MCC (3%) was confirmed by the meta-analysis of BRCA1/2 variants in the literature. Among the 915 MCC from 13 published series studied for molecular alterations of BRCA1/2, only 12 BRCA1/2 pathogenic mutations were identified (1À2% of MCC), whereas many other BRCA1/2 variants were variants of unknown significance or benign. BRCA1/2 pathogenic variants are uncommon in MCC. However, in BRCA-mutated MCC, poly-(ADP-Ribose)-polymerase inhibitors might be a valuable therapeutic option requiring validation by clinical trials

Soft tissue angiomatosis: another PIK3CA ‐related disorder

International audienceAIM:Angiomatosis of soft tissue (AST) is a, rare, high-flow, intramuscular vascular anomaly. In the context of PTEN hamartoma tumor syndrome (PHTS), this AST is referred to as PTEN hamartoma of soft tissue. Given that AST is observed in patients with no history of PHTS, we hypothesized that non-syndromic AST arises as a consequence of a somatic mutation.METHODS AND RESULTS:Thirteen patients with histologically confirmed AST were retrospectively studied. Details of the patients' personal and family medical histories and symptoms were retrieved from their medical records. The histological analyses were reviewed, and a tissue sample was used for genetic testing. Somatic mutations in the PIK3CA gene (p.Glu542Lys; p.Glu545Lys; p.His1047Arg) were identified in the tissue samples from seven patients, all of whom had unremarkable medical histories and had presented with a single lesion located in the lower limb. Five pathogenic variations in the PTEN gene (mutations: p.Lys263Arg; c.1026+2T>A; p.Ala126Thr; p.Leu108Arg; deletion, log ratio -0.55) were identified in the lesions of four patients; two of the latter had multifocal lesions. All four patients displayed macrocephaly, three boys presented with penile freckles, but none had a family history of PHTS. There were no histological differences between the PIK3CA and PTEN groups.CONCLUSIONS:AST can be related to either PTEN or PIK3CA mutations and may be multifocal in PHTS. AST appears to be a manifestation of PHTS that occurs in early childhood. The patient's medical history and clinical presentation should prompt the physician to perform specific genetic testing

Clinicopathologic and molecular analyses of cutaneous leiomyosarcoma: A retrospective, multicenter study of 79 cases

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[18F] FDOPA standardized uptake values of brain tumors are not exclusively dependent on LAT1 expression

<div><p>[18F]-FDOPA is a labeled amino acid (AA) analog used for positron emission tomography (PET) which is gaining increasing interest in the evaluation of brain tumors (BT). The AA-transporter LAT1 has been shown to be involved in [18F]-FDOPA uptake. The aim of this study was to determine whether the [18F]-FDOPA uptake was correlated with level of LAT1 expression in BT. Twenty-eight BT (including 19 gliomas and 9 metastases) were investigated by [18F]-FDOPA-PET prior to surgery and by anti-LAT1 immunohistochemistry on surgical specimens. The quantitative [18F]-FDOPA measured parameters were SUVmax, SUVmean and SUVpeak. LAT1 expression was quantified using a score (0 to 400). A significant [18F]-FDOPA uptake was associated with a LAT1 score ≥ 100 (p = 0.02) but there was no linear correlation between intensity of [18F]-FDOPA uptake and score of LAT1 expression whatever the parameters considered. LAT1 expression alone is not sufficient to explain variation of intensity of [18F]-FDOPA uptake in BT.</p></div

Relation between intervals from treatment to PET scan and parameters of [18F] FDOPA uptake.

<p>Relation between intervals from treatment to PET scan and parameters of [18F] FDOPA uptake.</p

Correlation between LAT1 scores and [18F] FDOPA standardized uptake values.

<p>a) correlation between LAT1 scores and SUVmax of tumours. b) correlation between LAT1 scores and ratio SUVmax T/S.</p

Histological characteristics and expression of LAT1 in brain tumours.

<p>Histological characteristics and expression of LAT1 in brain tumours.</p

LAT1 immunolabelling (x400).

<p>Diffuse and strong LAT1 expression in a small cell glioblastoma (a) and in a metastasis of ovary adenocarcinoma (b). Weak LAT1 expression in a glioblastoma (c) and in a metastasis of lung adenocarcinoma (d). Note LAT1 expression in endothelial cells (c).</p

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting

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