Myoepithelial carcinoma with RB1 mutation: remarkable chemosensitivity to carcinoma of unknown origin therapy

Hoggard, Timothy M.; Henderson-Jackson, Evita; Caracciolo, Jamie T.; Teer, Jamie K.; Yoder, Sean; Binitie, Odion; Gonzalez, Ricardo J.; Brohl, Andrew S.; Reed, Damon R.

doi:10.1186/s12885-017-3249-x

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…Our findings are in keeping with a previous case report of a soft tissue MEC interrogated via targeted sequencing, which found a low mutation burden (1 mutation/ Mb) and no alterations in known cancer genes, except for a frameshift in MAP3K6 (Stevens et al 2018). Conversely, in the only published case of a soft tissue MEC interrogated through WES, albeit without a germline control, truncating mutations in tumor suppressor genes RB1 and MED12 were identified (Hoggard et al 2017). Our WGS analysis here additionally demonstrates that loss of tumor suppressors in MECs may result from complex structural events, the spectra of which are as yet uncharacterized in MECs.…”

Section: Discussionsupporting

confidence: 91%

Whole-genome characterization of myoepithelial carcinomas of the soft tissue

Cyrta

Rosiene

Bareja

et al. 2022

Cold Spring Harb Mol Case Stud

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Myoepithelial carcinomas (MECs) of soft tissue are rare and aggressive tumors affecting young adults and children, but their molecular landscape has not been comprehensively explored through genome sequencing. Here, we present the whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing findings of two MECs. Patients 1 and 2 (P1, P2), both male, were diagnosed at 27 and 37 yr of age, respectively, with shoulder (P1) and inguinal (P2) soft tissue tumors. Both patients developed metastatic disease, and P2 died of disease. P1 tumor showed a rhabdoid cytomorphology and a complete loss of INI1 (SMARCB1) expression, associated with a homozygousSMARCB1deletion. The tumor from P2 showed a clear cell/small cell morphology, retained INI1 expression and strong S100 positivity. By WES and WGS, tumors from both patients displayed low tumor mutation burdens, and no targetable alterations in cancer genes were detected. P2's tumor harbored anEWSR1::KLF15rearrangement, whereas the tumor from P1 showed a novelASCC2::GGNBP2fusion. WGS evidenced a complex genomic event involving mainly Chromosomes 17 and 22 in the tumor from P1, which was consistent with chromoplexy. These findings are consistent with previous reports ofEWSR1rearrangements (50% of cases) in MECs and provide a genetic basis for the loss of SMARCB1 protein expression observed through immunohistochemistry in 10% of 40% of MEC cases. The lack of additional driver mutations in these tumors supports the hypothesis that these alterations are the key molecular events in MEC evolution. Furthermore, the presence of complex structural variant patterns, invisible to WES, highlights the novel biological insights that can be gained through the application of WGS to rare cancers.

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Section: Discussionsupporting

confidence: 91%

Whole-genome characterization of myoepithelial carcinomas of the soft tissue

Cyrta

Rosiene

Bareja

et al. 2022

Cold Spring Harb Mol Case Stud

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“…Table 3 shows previous published reports of soft tissue myoepithelial carcinoma. A previous case report has documented a partial response to carboplatin and paclitaxel in a patient with metastatic disease, treated with complete cytoreductive surgery following chemotherapy [9]. There are also currently no putative prognostic biomarkers for myoepithelial carcinoma; however, further study into the EWSR1 gene rearrangement [2], deletions of SMARCB1 [5] and their downstream pathways may be helpful in building a greater understanding of myoepithelial carcinoma pathogenesis and developing effective therapeutic agents.…”

Section: Yearsmentioning

confidence: 99%

Adult soft tissue myoepithelial carcinoma: treatment outcomes and efficacy of chemotherapy

et al. 2019

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Soft tissue myoepithelial carcinomas are a rare, malignant subgroup of myoepithelial tumours mostly arising in the extremities with equal predilection for women and men. The mainstay of management of localised disease is complete surgical resection. Despite optimal treatment, 40-45% of tumours recur. Data regarding the efficacy of systemic therapy for advanced and metastatic disease are lacking. The primary aim of this study was to evaluate the outcome of all patients with soft tissue myoepithelial carcinoma treated at a single referral centre. The secondary aim was to establish the efficacy of systemic therapies in patients with advanced disease. A retrospective review of the prospectively maintained Royal Marsden Sarcoma Unit database was performed to identify soft tissue myoepithelial carcinoma patients treated between 1996 and 2019. Patient baseline characteristics and treatment history were recorded. Response to systemic therapy was evaluated using RECIST 1.1. We identified 24 patients treated at our institution between 1996 and 2019,12 males and 12 females. Median age at presentation was 49.6 years [interquartile range (IQR) 40.5-63.3 years]. Twenty-two out of 24 patients (91.7%) underwent primary surgical resection. Nine patients (37.5%) received systemic treatment. A partial response was documented in one patient treated with doxorubicin. The median progression-free survival for first-line chemotherapy was 9.3 months. Myoepithelial carcinoma frequently recurs after complete surgical resection. Conventional chemotherapy demonstrated some activity in myoepithelial carcinoma, however, more effective systemic therapies are required and enrolment in clinical trial should be encouraged.

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“…Immunohistochemically, the tumor showed loss of INI1 with no rearrangement of either EWSR1 or FUS on fluorescence in situ hybridization, and partial response was achieved by systemic administration of doxorubicin. Hoggard et al also reported a case of metastatic MEC showing partial response to carboplatin and paclitaxel with a disease-free interval of more than 3 years ( 15 ). In that case, molecular analysis of the tumor was notably negative for rearrangement of the EWSR1 (22q12) locus.…”

Section: Discussionmentioning

confidence: 99%

Combination chemotherapy of doxorubicin and ifosfamide with proton beam therapy for myoepithelial carcinoma originating in the paraspinal region: A case report and literature review

et al. 2022

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Soft tissue myoepithelial carcinoma (MEC) is an extremely rare mesenchymal tumor that has a poor prognosis unless complete surgical resection is achieved. The present study reported a case of a 38-year-old woman with a tumor in the left paraspinal region at L2 to L3 with vertebral destruction. MEC was diagnosed based on molecular pathological examination of a biopsy specimen. Because curative surgery was expected to be difficult, a combination of chemotherapy with doxorubicin and ifosfamide and proton beam therapy as local therapy was performed, resulting in long-term survival for at least 7.8 years. To the best of our knowledge, this is the first case of soft tissue MEC for which classical cytotoxic chemotherapy and proton beam therapy were effective. Although surgical resection with negative margins is the mainstay of treatment for MEC, adequate doxorubicin-based systemic therapy and high-dose radiation therapy may be a feasible alternative in patients with unresectable or advanced MEC. Future studies on the relationship between molecular pathological features, including biomarkers, and the selection of therapeutic agents are warranted.

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Myoepithelial carcinoma with RB1 mutation: remarkable chemosensitivity to carcinoma of unknown origin therapy

Cited by 9 publications

References 28 publications

Whole-genome characterization of myoepithelial carcinomas of the soft tissue

Whole-genome characterization of myoepithelial carcinomas of the soft tissue

Adult soft tissue myoepithelial carcinoma: treatment outcomes and efficacy of chemotherapy

Combination chemotherapy of doxorubicin and ifosfamide with proton beam therapy for myoepithelial carcinoma originating in the paraspinal region: A case report and literature review

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