Citations 2
Genomic Microsatellite Signatures Identify Germline Mismatch Repair Deficiency and Risk of Cancer Onset
Chung, Jiil , Negm, Logine , Bianchi, Vanessa , Das, Anirban , Liu, Zhihui Amy , Sudhaman, Sumedha, Aronson, Melyssa , Brunga, Ledia , Forster, Victoria J. , Komosa, Martin, Davidson, Scott , Lees, Jodi, Tomboc, Patrick , Samuel, David , Bendel, Anne , Knipstein, Jeffrey , Schneider, Kami Wolfe , Reschke, Agnes , Zelcer, Shayna , Zorzi, Alexandra P., Bedgood, Raymond , Peterson, Lindsay L. , Rhode, Sara , Damme, An Van , Scheers, Isabelle , Robbins, Gabriel , Vanan, Magimairajan , Burke, Carol A. , Villani, Anita , Malkin, David , Durno, Carol , Hawkins, Cynthia , Maruvka, Yosef E. , Tabori, Uri , Das, Anirban , Aronson, Melyssa , Forster, Victoria , Davidson, Scott , Tomboc, Patrick , Knipstein, Jeffrey , Schneider, Kami Wolfe , Reschke, Agnes , McWilliams, Robert R , Foulkes, William D , Bedgood, Raymond , Peterson, Lindsay , Van Damme, An , Robbins, Gabriel , Vanan, Magimairajan Issai , Meyn, M Stephen , Auer, Rebecca , Leach, Brandie , Villani, Anita , Malkin, David , Bouffet, Eric , Hawkins, Cynthia , Maruvka, Yosef E , Tabori, Uri , Burke, Carol A , Stengs, Lucie K. , Sudhaman, Sumedha , Edwards, Melissa , Farah, Roula Antoine , McWilliams, Robert R. , Foulkes, William D. , Gardner, Sharon L , Bouffet, Éric , Huang, Annie , Taylor, Michael D. , Shlien, Adam , Getz, Gad
Journal of Clinical Oncology | October 14, 2022 | Volume: 41 | Issue: 4 | Pages: 766-777
PURPOSE Diagnosis of Mismatch Repair Deficiency (MMRD) is crucial for tumor management and early detection in patients with the cancer predisposition syndrome constitutional mismatch repair deficiency (CMMRD). Current diagnostic tools are cumbersome and inconsistent both in childhood cancers and in determining germline MMRD. PATIENTS AND METHODS We developed and analyzed a functional Low-pass Genomic Instability Characterization (LOGIC) assay to detect MMRD. The diagnostic performance of LOGIC was compared with that of current established assays including tumor mutational burden, immunohistochemistry, and the microsatellite instability panel. LOGIC was then applied to various normal tissues of patients with CMMRD with comprehensive clinical data including age of cancer presentation. RESULTS Overall, LOGIC was 100% sensitive and specific in detecting MMRD in childhood cancers (N = 376). It was more sensitive than the microsatellite instability panel (14%, P = 4.3 × 10 −12 ), immunohistochemistry (86%, P = 4.6 × 10 −3 ), or tumor mutational burden (80%, P = 9.1 × 10 −4 ). LOGIC was able to distinguish CMMRD from other cancer predisposition syndromes using blood and saliva DNA ( P < .0001, n = 277). In normal cells, MMRDness scores differed between tissues (GI > blood > brain), increased over time in the same individual, and revealed genotype-phenotype associations within the mismatch repair genes. Importantly, increased MMRDness score was associated with younger age of first cancer presentation in individuals with CMMRD ( P = 2.2 × 10 −5 ). CONCLUSION LOGIC was a robust tool for the diagnosis of MMRD in multiple cancer types and in normal tissues. LOGIC may inform therapeutic cancer decisions, provide rapid diagnosis of germline MMRD, and support tailored surveillance for individuals with CMMRD.
DNAJB1‐PRKACA–positive metastatic fibrolamellar carcinoma with unknown primary in a pediatric patient
Balbeur, Samuel , Dumortier, Adeline, Mergen, Julien, Libbrecht, Louis , Boulanger, Cécile , Goyet, Maëlle de Ville de , Damme, An Van , Boulanger, Cecile , de Ville de Goyet, Maelle , Van Damme, An , Torbenson, Michael , Brichard, Bénédicte
Pediatric Blood & Cancer | November 18, 2019 | Volume: 67 | Issue: 2 | Pages: No page available
AbstractFibrolamellar carcinoma (FLC) is a rare variant of hepatocellular carcinoma, occurring in children and young adults without underlying liver disease. The diagnosis is based on morphological characteristics of the tumor, supplemented by immunohistochemistry and/or genetic testing. Recently, the presence of a characteristic DNAJB1‐PRKACA fusion gene has been associated with FLC. Herein, we report a case of FLC presenting as peritoneal carcinomatosis in a 14‐year‐old female. Interestingly, no liver tumor was seen on imaging, and an alternative possibility is that the tumor arose outside the liver as a hepatoid carcinoma with fibrolamellar features.