المؤلفون: Leroy, Karen, Audigier Valette, Clarisse, Alexandre, Jérôme, Boussemart, Lise, Chiesa, Jean, Deldycke, Clotilde, Gomez-Rocca, Carlos, Hollebecque, Antoine, Lehmann-Che, Jacqueline, Lemoine, Antoinette, Mansard, Sandrine, Medioni, Jacques, Monnet, Isabelle, Mourah, Samia, Pierret, Thomas, Spaëth, Dominique, Civet, Alexandre, Galoin, Sandrine, Italiano, Antoine

المساهمون: Yamano, Tomoki, Roche

المصدر: PLOS ONE ; volume 18, issue 9, page e0291495 ; ISSN 1932-6203

الوصف: Introduction Considering the growing interest in matched cancer treatment, our aim was to evaluate the ability of a comprehensive genomic profiling (CGP) assay to propose at least one targeted therapy given an identified genomic alteration or signature (actionability), and to collect the treatment modifications based on the CGP test results in clinical practise for solid tumors. Methods This retrospective, multicentre French study was conducted among 25 centres that participated in a free of charge program between 2017 and 2019 for a tissue CGP test. Data were collected on the patient, disease, tumor genomic profile, treatment suggested in the report (related to the genomic profile results) and subsequent therapeutic decisions according to the physician’s declaration. Results Among the 416 patients, most had lung cancer (35.6%), followed by biliary tract cancer (11.5%) or rare cancers (11.1%); 75% had a metastatic disease. The actionability was 75.0% (95% CI [70.6%-78.9%]) for all patients, 85.1% and 78.4%, respectively in lung cancer and metastatic patients. After exclusion of clinical trial suggestions, the actionability decreased to 62.3% (95% CI [57.5%-66.8%]). Treatment modification based on the test results was observed in 17.3% of the patients and was more frequent in metastatic disease (OR = 2.73, 95% CI [1.31–5.71], p = 0.007). The main reasons for no treatment modification were poor general condition (33.2%) and stable disease or remission (30.2%). The genomic-directed treatment changes were performed mostly during the first six months after the CGP test, and interestingly a substantial part was observed from six to 24 months after the genomic profiling. Conclusion This French study provides information on the real-life actionability of a CGP test based on tissue samples, and trends to confirm its utility in clinical practice across the course of the disease, in particularly for patients with lung cancer and/or advanced disease.

الإتاحة: https://doi.org/10.1371/journal.pone.0291495Test

المؤلفون: Thériault, Catherine, Galoin, Sandrine, Valmary, Severine, Selves, Janick, Lamant, Laurence, Roda, Daniel, Rigal-Huguet, Françoise, Brousset, Pierre, Delsol, Georges, Al Saati, Talal

المصدر: Modern Pathology ; volume 13, issue 12, page 1269-1279 ; ISSN 0893-3952

مصطلحات موضوعية: Pathology and Forensic Medicine

الإتاحة: https://doi.org/10.1038/modpathol.3880232Test
http://www.nature.com/articles/3880232.pdfTest
http://www.nature.com/articles/3880232Test
https://api.elsevier.com/content/article/PII:S0893395222038753?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0893395222038753?httpAccept=text/plainTest

المؤلفون: Galoin, Sandrine, Daste, Ghislaine, Apoil, Paul‐André, Chollet, François, Roda, Daniel, Blancher, Antoine, Delsol, Georges, Chittal, Shashikant, Al Saati, Talal

المصدر: British Journal of Haematology ; volume 99, issue 1, page 122-130 ; ISSN 0007-1048 1365-2141

الوصف: In the search of B‐cell lymphoma/leukaemia dissemination to cerebrospinal fluid (CSF), we used the highly sensitive semi‐nested PCR (snPCR) for the analysis of IgH gene rearrangements. This method detects a rearranged IgH gene from a single B lymphocyte which may or may not represent the neoplastic B‐cell population. We therefore performed multiple snPCR (three to five) experiments on the same CSF sample, postulating that the detection of a band of the same size and sequence in different PCR runs was highly indicative of a clonal population. 17 consecutive cases with a differential diagnosis of primary (P cns L) ( n =10) or secondary (S cns L) ( n =7) CNS lymphoma or leukaemia were investigated by the new strategy. The clonal nature of the B‐cell population was confirmed in 3/10 of suspected P cns L, and in six other cases the PCR study was indicative of reactive lymphocytosis. One case revealed a clonal B‐cell population in the clinical context of an autoimmune disorder. Evidence of clonal B‐cell population was found in 4/7 of suspected S cns L. In one of these cases the detected band and its sequence proved identical to that of the primary nodal lymphoma. We believe that the evaluation of B‐cell clonality in CSF requires multiple snPCR amplification on the same sample to compare the size of the products and, if necessary, the DNA sequences to ascertain the diagnosis of malignancy in equivocal cytologic and clinical findings.

الإتاحة: https://doi.org/10.1046/j.1365-2141.1997.3423153.xTest

المؤلفون: AL SAATI, TALAL, GALOIN, SANDRINE, GRAVEL, SYLVIA, LAMANT, LAURENCE, RODA, DANIEL, CHITTAL, SHASHIKANT M., DELSOL, GEORGES

المصدر: The Journal of Pathology ; volume 181, issue 4, page 387-393 ; ISSN 0022-3417 1096-9896

الإتاحة: https://doi.org/10.1002Test/(sici)1096-9896(199704)181:4%3C387::aid-path781%3E3.0.co%3B2-u

المؤلفون: Galoin, Sandrine, Al Saati, Talal, Schlaife r, Daniel, Huynh, Anne, Attal, Michel, Delsol, Georges

المصدر: British Journal of Haematology ; volume 94, issue 4, page 676-684 ; ISSN 0007-1048 1365-2141

الوصف: Follicular lymphomas are often associated with t(14;18) chromosomal translocation. The rearrangement site ( bcl ‐2/ J H junctional region) between the two chromosomes is hypervariable regarding its size and DNA sequence, and is a potential specific marker for the neoplastic clone of each patient. We report the use of the polymerase chain reaction (PCR) technique for detecting and sequencing clonal bcl ‐2/ J H rearrangements in lymph nodes and/or bone marrow specimens from patients with follicular lymphoma. 53 patients at diagnosis ( n = 40) or at relapse ( n = 13) were studied. 25 of these 53 cases were found to have the t(14;18) translocation involving either the major breakpoint region (MBR) ( n =21) or the minor cluster region (mcr) ( n = 4). Since our PCR technique could detect the translocation in 1/10 6 cells we had to distinguish mal‐ignant cells from possible t(14;18)‐bearing non‐malignant cells which could be present during and after treatment. The bcl ‐2/ J H junctional regions were therefore sequenced in order to synthesize an anti‐junction oligonucleotide probe specific for each patient’s malignant clone (clonospecific probe). Using these clonospecific probes for hybridization it was possible to detect one malignant cell mixed with 10 6 normal cells. 28 patients with advanced stage (stage III and IV), had been enrolled for treatment with myeloablative chemoradiotherapy and autologous bone marrow transplantation (ABMT). In 12 of these patients bcl ‐2/MBR translocation was found at diagnosis and used as a marker to detect the presence of residual lymphoma cells in serial bone marrow (BM) and peripheral blood (PB) samples. In three relapsed patients (with available tissue samples at diagnosis and relapse), clonospecific probes clearly demonstrated the same bcl ‐2/ J H junction, thus confirming that the relapse occurred from the same malignant clone, and which remained stable without any clonal evolution of its junctional region throughout the course of the disease. These results demonstrate the value of ...

الإتاحة: https://doi.org/10.1046/j.1365-2141.1996.7062323.xTest

المؤلفون: Thériault, Catherine, Galoin, Sandrine, Valmary, Severine, Selves, Janick, Lamant, Laurence, Roda, Daniel, Rigal-Huguet, Françoise, Brousset, Pierre, Delsol, Georges, Saati, Talal Al

المصدر: Modern Pathology; Dec2000, Vol. 13 Issue 12, p1269-1279, 11p

المؤلفون: AL SAATI, TALAL, GALOIN, SANDRINE, GRAVEL, SYLVIA, LAMANT, LAURENCE, RODA, DANIEL, CHITTAL, SHASHIKANT M., DELSOL, GEORGES

المصدر: Journal of Pathology; 1997, Vol. 181 Issue 4, p387-393, 7p

المؤلفون: SAATI, TALAL AL, GALOIN, SANDRINE, GRAVEL, SYLVIA, LAMANT, LAURENCE, RODA, DANIEL, CHITTAL, SHASHIKANT M., DELSOL, GEORGES

المصدر: The Journal of Pathology; April 1997, Vol. 181 Issue: 4 p387-393, 7p

مستخلص: Analysis of IgH and TcR-γ genes using consensus primers identifying junctional regions of rearranged genes by polymerase chain reaction (PCR) was performed on tissues involved by Hodgkin's disease (HD) in 90 cases and was correlated with the immunophenotype of Hodgkin and Reed–Sternberg (HRS) cells and the presence of Epstein–Barr virus (EBV) within these cells. Clonal IgH gene rearrangements were found in 1/5 cases of lymphocyte predominance (LP) subtype and none was positive for EBV. In 85 cases of classic HD, no IgH or TcR-γ gene rearrangements were found in 51 (60 per cent) cases. A similar percentage, but not the same cases, were of null (non-B, non-T) phenotype. Of 30 cases where a B phenotype was assigned to HRS cells, nine had IgH gene rearrangements, three had TcR-γ gene rearrangements, and two had both genes rearranged. None of the five cases assigned to T phenotype of HRS cells showed rearrangement of TcR-γ genes, but two cases showed rearranged IgH genes. Among 41 cases of null phenotype, ten had IgH gene rearrangements, five had TcR-γ gene rearrangements, and three cases had both genes rearranged. Whereas EBV was detectable in HRS cells in 17/43 classic HD cases of assigned B phenotype, EBV was also detectable in 2/5 cases of assigned T phenotype and in 21 cases with the null phenotype. Furthermore, there was no correlation of EBV with the presence or lack of IgH or TCR-γ gene rearrangements. Of the remainder, half (30 per cent) expressed antigens associated with lymphocytes without an appropriate genotype. The results confirm lymphocyte-lineage committed cells at the origin of HRS cells in 40 per cent of cases. Any hypothesis of a non-lymphocytic origin of HRS cells will require the inducibility of CD30 on candidate precursors and the methodology for probing genetic events in such cells to be addressed. © 1997 by John Wiley & Sons, Ltd.