bims-lifras 2024-04-14 papers

Issue of 2024–04–14
three papers selected by
Joanna Zawacka, Karolinska Institutet

J Clin Med. 2024 Feb 21. pii: 1223. [Epub ahead of print]13(5):

Whole-Body MRI Screening for Carriers of Germline TP53 Mutations-A Systematic Review and Meta-Analysis.

Hugo C Temperley, Niall J O'Sullivan, Benjamin M Mac Curtain, Wanyang Qian, Tatiana S Temperley, Alannah Murray, Alison Corr, Ian Brennan, David Gallagher, James F Meaney, Michael E Kelly.

PURPOSE: This systematic review evaluated whole-body MRI (WB-MRI) as a cancer screening tool for individuals carrying germline TP53 mutations, a population known to be at a significantly elevated risk of malignancy. The primary objective is to assess the diagnostic performance of WB-MRI in detecting cancer in this cohort.
METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials were searched until 18 August 2023. Eligible studies were selected based on predefined inclusion criteria. The data extracted included information on study characteristics, patient demographics, and the WB-MRI diagnostic performance.
RESULTS: This systematic review identified eight eligible studies, comprising 506 TP53 mutation carriers. The mean age was 34.6 ± 16.3 (range 1-74) years. In total, 321/506 (63.4%) of the patients were female and 185/506 (36.6%) were male. In addition, 267/506 (52.8%) had a previous oncological diagnosis. Thirty-six new cancers were diagnosed with WB-MRI (36/506 (7.1%)). The overall pooled proportion of cancer detected on MRI was 7% (95% confidence interval 5-10). In total, 44 new lesions were picked up, as multiple lesions were found in some patients.
CONCLUSION: WB-MRI is an effective cancer screening tool for TP53 mutation carriers. While these findings suggest the potential for WB-MRI to contribute to early cancer detection in this high-risk population, further research and the standardisation of protocols internationally are warranted to optimise its clinical utility.

Keywords: Li-Fraumeni syndrome; TP53 mutations; cancer screening; whole-body MRI

DOI: https://doi.org/10.3390/jcm13051223

Acta Neuropathol Commun. 2024 Apr 11. 12(1): 57

Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases.

Yuji Kibe, Fumiharu Ohka, Kosuke Aoki, Junya Yamaguchi, Kazuya Motomura, Eiji Ito, Kazuhito Takeuchi, Yuichi Nagata, Satoshi Ito, Nobuhiko Mizutani, Yoshiki Shiba, Sachi Maeda, Tomohide Nishikawa, Hiroki Shimizu, Ryuta Saito.

Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene. Central nervous system tumors, such as choroid plexus tumors, medulloblastomas, and diffuse gliomas, are frequently found in patients with LFS. Although molecular profiles of diffuse gliomas that develop in pediatric patients with LFS have been elucidated, those in adults are limited. Recently, diffuse gliomas have been divided into pediatric- and adult-type gliomas, based on their distinct molecular profiles. In the present study, we investigated the molecular profiles of high-grade gliomas in three adults with LFS. These tumors revealed characteristic histopathological findings of high-grade glioma or glioblastoma and harbored wild-type IDH1/2 according to whole exome sequencing (WES). However, these tumors did not exhibit the key molecular alterations of glioblastoma, IDH-wildtype such as TERT promoter mutation, EGFR amplification, or chromosome 7 gain and 10 loss. Although WES revealed no other characteristic gene mutations or copy number alterations in high-grade gliomas, such as those in histone H3 genes, PDGFRA amplification was found in all three cases together with uniparental disomy of chromosome 17p, where the TP53 gene is located. DNA methylation analyses revealed that all tumors exhibited DNA methylation profiles similar to those of pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (pHGG H3-/IDH-wt), RTK1 subtype. These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.

Keywords: PDGFRA amplification; H3-wildtype and IDH-wildtype; Li-Fraumeni syndrome; Pediatric-type high-grade glioma

DOI: https://doi.org/10.1186/s40478-024-01762-7

Front Oncol. 2024 ;14 1364199

Case report: Therapy-related myeloid neoplasms in three pediatric cases with medulloblastoma.

Li Shun Mak, Xiuling Li, Wilson Y K Chan, Alex W K Leung, Daniel K L Cheuk, Liz Y P Yuen, Jason C C So, Shau Yin Ha, Anthony P Y Liu.

Introduction: Medulloblastoma is the most common malignant brain tumor in children, often requiring intensive multimodal therapy, including chemotherapy with alkylating agents. However, therapy-related complications, such as therapy-related myeloid neoplasms (t-MNs), can arise, particularly in patients with genetic predisposition syndromes. This case report presents three pediatric cases of medulloblastoma with subsequent development of t-MNs, highlighting the potential role of genetic predisposition and the importance of surveillance for hematological abnormalities in long-term survivors.
Case presentation: We describe three cases of pediatric medulloblastoma who developed t-MNs after receiving chemotherapy, including alkylating agents. Two of the patients had underlying genetic predisposition syndromes (TP53 pathologic variants). The latency period between initial diagnosis of medulloblastoma and the development of secondary cancer varied among the cases, ranging from 17 to 65 months. The three cases eventually succumbed from secondary malignancy, therapy-related complications and progression of primary disease, respectively.
Conclusions: This report highlights the potential association between genetic predisposition syndromes and the development of therapy-related myeloid neoplasms in pediatric medulloblastoma survivors. It underscores the importance of surveillance for hematological abnormalities among such patients.

Keywords: Li-Fraumeni syndrome; alkylating agent; case report; chemotherapy; genetic predisposition; medulloblastoma (MB); therapy-related myelodysplastic syndrome/acute myeloid leukemia

DOI: https://doi.org/10.3389/fonc.2024.1364199