A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review

Our plain-English summary of A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review, by C. Miyagawa, H. Takaya, K. Sakai, et al (The Oncologist, 2021).

The study

• Authors: C. Miyagawa, H. Takaya, K. Sakai, K. Nishio, M. Konishi, S. Minamiguchi, T. Shimada, N. Matsumura
• Journal: The Oncologist
• Published: 2021;26(5):356-361
• Type of article: Case report, Review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Recently, several malignant peritoneal mesotheliomas (MPMs), occurring in young women without asbestos exposure and with fusion genes such as anaplastic lymphoma kinase (ALK) and Ewing sarcoma breakpoint region 1, have been reported. In the present case, we encountered MPM with STRN-ALK fusion in a 17-year-old female adolescent. The case did not respond to chemotherapy and is currently in a clinical trial of alectinib. This is the fourth reported case of MPM with STRN-ALK fusion. Of the 45 cancer cases with STRN-ALK fusion in which the fusion partners were examined, all cases except for the current case showed fusion of exon 3 of STRN and exon 20 of ALK. This is the first case with fusion of exon 2 of STRN and exon 20 of ALK. Further advances in cancer genomic medicine may help clarify the clinical significance of this new fusion. KEY POINTS: Malignant peritoneal mesotheliomas (MPMs) can occur in young women without asbestos exposure and show fusion genes that activate anaplastic lymphoma kinase (ALK) by gene rearrangement. ALK rearrangement and the fusion partner can be detected by companion diagnostics and by next generation sequencing. Patients with MPMs with ALK rearrangement may benefit from target therapy.

© 2021 AlphaMed Press.

In plain English

This article was a case report with a literature review, written by doctors in Japan. It described a 17-year-old Japanese girl who came to hospital short of breath. She had no history of asbestos exposure. Tissue taken by laparoscopy was diagnosed as malignant peritoneal mesothelioma, a cancer of the abdominal lining. Testing found a change in the ALK gene in 86% of tumor cells. RNA sequencing showed exon 2 of the STRN gene joined to exon 20 of ALK. The authors reported that in the 45 published cancers where the joining point had been examined, all 44 others joined STRN exon 3 instead. They counted eight reported peritoneal mesotheliomas with ALK changes, including this one, and none of those patients had a history of asbestos exposure. Standard chemotherapy did not stop her tumor from growing, and she entered a clinical trial of the drug alectinib. Whether she would respond was not yet known. The authors concluded that further advances in cancer genomic medicine may help clarify what this new gene fusion means clinically.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report of one patient, with a literature review of previously reported cancers carrying the STRN-ALK gene fusion
• Who was studied: One 17-year-old Japanese girl treated at a hospital in Japan who presented with shortness of breath (dyspnea). The literature review covered previously published cases of cancers with the STRN-ALK fusion.
• Exposure: No asbestos exposure. The patient had no history of asbestos exposure. The study concerned a gene fusion (STRN-ALK) in the tumor, not an asbestos exposure.
• Main results:
  • In this patient, tissue examination showed biphasic epithelial malignant peritoneal mesothelioma.
  • In this patient, the blood marker carbohydrate antigen 125 was elevated at 990 U/mL (normal less than 35 U/mL).
  • In this patient's tumor, fluorescence in situ hybridization (FISH) showed 86% of cells positive for ALK fusion. The EWSR1 fusion gene was negative.
  • In this patient's tumor, RNA sequencing showed STRN exon 2 fused to ALK intron 19 (ALK exon 20 in the coding region).
  • The authors described the staining pattern of this patient's tumor as having the characteristics of an asbestos-free peritoneal mesothelioma.
  • Literature review: eight peritoneal mesothelioma cases with ALK translocation had been reported, including this one, and none of those patients had a history of asbestos exposure. Seven were female, and age at onset was 10 to 51 years (median 17).
  • Literature review: 56 cancer cases with STRN-ALK had been reported worldwide, including this one: 4 peritoneal mesothelioma, 41 thyroid, 5 lung, 3 colorectal, 2 renal and 1 pancreatic cancer.
  • Literature review: the fusion site had been studied in 45 cases. All except the present case (n = 44) had STRN exon 3 fused to ALK exon 20.
  • The patient's tumor progressed despite pemetrexed plus cisplatin (7 cycles) and carboplatin plus gemcitabine (3 cycles). She then joined a phase II clinical trial and was receiving alectinib.
• The authors' conclusion: The authors reported this as the first case with STRN exon 2 fused to ALK exon 20. They concluded that further advances in cancer genomic medicine may help clarify the clinical significance of this new fusion.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Asbestos Exposure, Sarcoma, Chemotherapy, Clinical Trial.

Related studies

• Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma — Y.P. Hung, F. Dong, et al. (2018)
• Anaplastic lymphoma kinase (ALK) translocation in paediatric malignant peritoneal mesothelioma: a case report of novel ALK-related tumour spectrum — K. Loharamtaweethong, N. Puripat, et al. (2016)
• Detection of Anaplastic Lymphoma Kinase-Rearranged Mesothelioma Cells in Ascites by Companion Diagnostics — M. Konishi, T. Kanyama, et al. (2020)
• A novel nomogram for peritoneal mesothelioma predicts survival — N.P. Schaub, M. Alimchandani, et al. (2013)
• Treating peritoneal mesothelioma with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. A case series and review of the literature — K. Stamou, D. Tsamis, et al. (2015)
• Exon deletion in the MSLN gene encoding MPF/mesothelin precursor protein during Laurasiatherian mammal evolution — D.S. Kim, Y. Hahn (2011)

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