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1. Pleuropulmonary blastoma (PPB) and other DICER1-associated high-grade malignancies are morphologically, genetically and epigenetically related – A comparative study of 4 PPBs and 6 sarcomas

Author

Hiemcke-Jiwa, L.S., van Belle, S., Eijkelenboom, A., Merks, J.H.M., van Noesel, M.M., Kaal, S.E.J., Pijnenborg, J.M.A., Bulten, J., Tops, B.B.J., van de Ven, C.P., van Gorp, J.M., de Krijger, R.R., Cheesman, E., Kelsey, A.M., Kester, L.A., and Flucke, U.

Published
2022
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2. JS01.3.A EPIGENETICALLY DEFINED ANGIOCENTRIC GLIOMAS MAY LACK ANGIOCENTRIC GROWTH AND INSTEAD SHOW A VARIETY OF GROWTH PATTERNS

Author

Stegat, L, primary, Rohwer, J L, additional, Stichel, D, additional, Schrimpf, D, additional, Coras, R, additional, Pagès, M, additional, Tauziède-Espariat, A, additional, Varlet, P, additional, Hans, V H, additional, Meyer, J, additional, Schittenhelm, J, additional, Staszewski, O, additional, Cheesman, E, additional, Glatzel, M, additional, Schmid, S, additional, Wesseling, P, additional, Korshunov, A, additional, Sexton-Oates, A, additional, Schüller, U, additional, Kõrgvee, L, additional, Mueller, S, additional, Olar, A, additional, Snuderl, M, additional, Schweizer, L, additional, Aronica, E, additional, Sahm, F, additional, von Deimling, A, additional, Blumcke, I, additional, Jones, D T W, additional, Capper, D, additional, and Wefers, A K, additional

Published
2023
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4. Pleuropulmonary blastoma (PPB) and other DICER1-associated high-grade malignancies are morphologically, genetically and epigenetically related - A comparative study of 4 PPBs and 6 sarcomas

Author

Pathologie Groep Van Diest, Cancer, PMC Medisch specialisten, Onderzoek Beeld, Pathologie Pathologen staf, Hiemcke-Jiwa, L S, van Belle, S, Eijkelenboom, A, Merks, J H M, van Noesel, M M, Kaal, Suzanne E.J., Pijnenborg, J M A, Bulten, J, Tops, B B J, van de Ven, C P, van Gorp, J M, de Krijger, R R, Cheesman, E, Kelsey, A M, Kester, L A, Nijmegen, Radboud, Pathologie Groep Van Diest, Cancer, PMC Medisch specialisten, Onderzoek Beeld, Pathologie Pathologen staf, Hiemcke-Jiwa, L S, van Belle, S, Eijkelenboom, A, Merks, J H M, van Noesel, M M, Kaal, Suzanne E.J., Pijnenborg, J M A, Bulten, J, Tops, B B J, van de Ven, C P, van Gorp, J M, de Krijger, R R, Cheesman, E, Kelsey, A M, Kester, L A, and Nijmegen, Radboud

Published
2022

6. Pleuropulmonary Blastoma (PPB) and Other DICER1-Associated High-Grade Malignancies are Morphologically, Genetically and Epigenetically Related – A Comparative Study of 4 PPBs and 6 Sarcomas

Author

Hiemcke-Jiwa, Laura, primary, van Belle, Sarah, additional, Eijkelenboom, A., additional, Merks, Johannes H. M., additional, van Noesel, M. M., additional, Kaal, S. E.J., additional, Pijnenborg, J. M.A., additional, Bulten, J., additional, Tops, B. B.J., additional, van de Ven, C. P., additional, van Gorp, J. M., additional, de Krijger, Ronald R., additional, Cheesman, E., additional, Kelsey, A. M., additional, Kester, L. A., additional, and Flucke, U., additional

Published
2022
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11. Intracranial angiomatoid fibrous histiocytoma with EWSR1-CREB family fusions:a report of two pediatric cases

Author

Konstantinidis, A, Cheesman, E, O'Sullivan, J, Pavaine, J, Avula, S, Pizer, B, and Kilday, J P

Abstract

BACKGROUND: Intracranial angiomatoid fibrous histiocytomas (AFHs) are very rare tumors. Histologically, classical cases have been reported exclusively in adults with only myxoid variants identified in children. Here, we report the clinical presentation, treatment, biopsy and molecular test results for two children with classical intracranial AFH and combine this with a literature review of published intracranial AFH and AFH-like cases.CASE DESCRIPTION: Two pediatric females, presenting with abnormal neurological signs, were diagnosed with intracranial AFHs from histopathological analysis. No myxoid features were identified. Fluorescence in situ hybridization (FISH) and Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) testing demonstrated EWS1-ATF1 and EWS1-CREM gene fusions respectively, verified by Sanger sequencing. Both patients underwent surgery only. The first child developed local recurrence five years from initial surgery. Following a further complete resection, this patient has remained recurrence-free over a subsequent six year follow-up period. The second patient has recently developed local multi-nodular recurrence 28 months after initial surgery and is awaiting surgical re-excision. No additional chemotherapy/radiotherapy has been administered to either patient.CONCLUSIONS: This paper describes the first two cases of non-myxoid intracranial AFH in children; confirmed by molecular analysis. Our results suggest that a tumor spectrum incorporating classical and myxoid intracranial AFHs can occur in children and that gross total resection represents the treatment strategy of choice at diagnosis or following recurrence.

Published
2019

17. Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers

Author

Egg, D, Schwab, C, Gabrysch, A, Arkwright, PD, Cheesman, E, Giulino-Roth, L, Neth, O, Snapper, S, Okada, S, Moutschen, M, Delvenne, P, Pecher, A-C, Wolff, D, Kim, Y-J, Seneviratne, S, Kim, K-M, Kang, J-M, Ojaimi, S, McLean, C, Warnatz, K, Seidl, M, Grimbacher, B, Egg, D, Schwab, C, Gabrysch, A, Arkwright, PD, Cheesman, E, Giulino-Roth, L, Neth, O, Snapper, S, Okada, S, Moutschen, M, Delvenne, P, Pecher, A-C, Wolff, D, Kim, Y-J, Seneviratne, S, Kim, K-M, Kang, J-M, Ojaimi, S, McLean, C, Warnatz, K, Seidl, M, and Grimbacher, B

Abstract

Background: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in CTLA4 can cause an immune dysregulation syndrome. The phenotype comprises a broad spectrum of autoinflammatory, autoimmune, and immunodeficient features. An increased frequency of malignancies in primary immunodeficiencies is known, but their incidence in CTLA-4 insufficiency is unknown. Methods: Clinical manifestations and details of the clinical history were assessed in a worldwide cohort of 184 CTLA4 mutation carriers. Whenever a malignancy was reported, a malignancy-specific questionnaire was filled. Results: Among the 184 CTLA4 mutation carriers, 131 were considered affected, indicating a penetrance of 71.2%. We documented 17 malignancies, which amounts to a cancer prevalence of 12.9% in affected CTLA4 mutation carriers. There were ten lymphomas, five gastric cancers, one multiple myeloma, and one metastatic melanoma. Seven lymphomas and three gastric cancers were EBV-associated. Conclusion: Our findings demonstrate an elevated cancer risk for patients with CTLA-4 insufficiency. As more than half of the cancers were EBV-associated, the failure to control oncogenic viruses seems to be part of the CTLA-4-insufficient phenotype. Hence, lymphoproliferation and EBV viral load in blood should be carefully monitored, especially when immunosuppressing affected CTLA4 mutation carriers.

Published
2018

31. An analysis of the interaction between mouse apolipoprotein B100 and apolipoprotein(a).

Author

Cheesman, E J, Sharp, R J, Zlot, C H, Liu, C Y, Taylor, S, Marcovina, S M, Young, S G, and McCormick, S P

Abstract

The assembly of lipoprotein(a) (Lp(a)) involves an initial noncovalent interaction between apolipoprotein (apo) B100 and apo(a), followed by the formation of a disulfide bond between apoB100 cysteine 4326 and apo(a) cysteine 4057. The structural features of apoB100 that are required for its noncovalent interaction with apo(a) have not been fully defined. To analyze that initial interaction, we tested whether apo(a) could bind noncovalently to two apoB proteins that lack cysteine 4326: mouse apoB100 and human apoB100-C4326G. Our experiments demonstrated that both mouse apoB and the human apoB100-C4326G bind noncovalently to apo(a). We next sought to gain insights into the apoB amino acid sequences required for the interaction between apoB100 and apo(a). Previous studies of truncated human apoB proteins indicated that the carboxyl terminus of human apoB100 (amino acids 4330-4397) is important for Lp(a) assembly. To determine whether the carboxyl terminus of mouse apoB100 can interact with apo(a), transgenic mice were produced with a mutant human apoB gene construct in which human apoB100 amino acids 4279-4536 were replaced with the corresponding mouse apoB100 sequences and tyrosine 4326 was changed to a cysteine. The mutant apoB100 bound to apo(a) and formed bona fide disulfide-linked Lp(a), but Lp(a) assembly was less efficient than with wild-type human apoB100. The fact that Lp(a) assembly was less efficient with the mouse apoB sequences provides additional support for the notion that sequences in the carboxyl terminus of apoB100 are important for Lp(a) assembly.

Published
2000
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