Comprehensive genomic analysis of primary malignant melanoma of the esophagus reveals similar genetic patterns compared with epithelium-associated melanomas

Li, Jingjing; Liu, Bing; Ye, Qing; Xiao, Xiao; Shi, Yan; Guan, Wenyan; Li, He; Wang, Changxi; Yu, Zicheng; Tai, Zaixian; Pei, Shimei; Ma, Yuanyuan; Li, Shaolei; Wang, Yaqi; Wu, Nan

doi:10.1038/s41379-022-01116-5

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…The mutational signature and driver genes reflect those reported by Li et al , who found that PMME had similar genomic patterns as cutaneous melanoma. 31 Overall, similar genomic patterns with cutaneous melanoma may explain why PMME exhibited a more favorable response to anti-PD-1 treatment than NEMM.…”

Section: Discussionmentioning

confidence: 92%

Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy

Dai

Bai

Gao

et al. 2023

J Immunother Cancer

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BackgroundAccumulating data suggest that mucosal melanoma, well known for its poor response to immune checkpoint blockade (ICB) and abysmal prognosis, is a heterogeneous subtype of melanoma with distinct genomic and clinical characteristics between different anatomic locations of the primary lesions. Primary malignant melanoma of the esophagus (PMME) is a rare, highly aggressive disease with a poorer prognosis compared with that of non-esophageal mucosal melanoma (NEMM). In this study, we retrospectively analyzed the efficacy of anti-programmed death (PD)-1 in patients with PMME and explored its molecular basis.MethodsThe response and survival of patients with PMME and NEMM under anti-PD-1 monotherapy were retrospectively analyzed. To explore the molecular mechanisms of the difference in therapeutic efficacy between PMME and NEMM, we performed genomic analysis, bulk RNA sequencing, and multiplex immunohistochemistry staining.ResultsWe found that PMME (n=28) responded better to anti-PD-1 treatment than NEMM (n=64), with a significantly higher objective response rate (33.3% (95% CI 14.3% to 52.3%) vs 6.6% (95% CI 0.2% to 12.9%)) and disease control rate (74.1% (95% CI 56.4% to 91.7%) vs 37.7% (95% CI 25.2% to 50.2%)). Genomic sequencing analysis revealed that the genomic aberration landscape of PMME predominated in classical cancer driver genes, with approximately half of PMME cases harboring mutations inBRAF,N/KRAS, andNF1. In contrast, most NEMM cases were triple wild-type. Transcriptome analysis revealed that, compared with NEMM, PMME displayed more significant proliferation and inflammatory features with higher expression of genes related to antigen presentation and differentiation, and a less immunosuppressive signature with lower expression of inhibitory immune checkpoints and dedifferentiation-related genes. The multiplex immunohistochemical analysis also demonstrated higher CD8+T-cell infiltration in PMME than in NEMM.ConclusionsPMME is an outlier of mucosal melanoma showing a malicious phenotype but a particularly high response rate to ICB because of its distinct molecular characteristics. Patient stratification based on anatomic origin can facilitate clinical decision-making in patients with mucosal melanoma following the verification of our results in future prospective studies.

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Section: Discussionmentioning

confidence: 92%

Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy

Dai

Bai

Gao

et al. 2023

J Immunother Cancer

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“…В ряде исследований мутационного профиля были выявлены мутации в генах BRAF, NRAS и KIT, однако первичный характер меланом не был доказан, и в изучаемую выборку могли быть включены пациенты с метастатическим поражением [22]. Также, в одном из исследований описаны геномные особенности первичных меланом пищевода, а также проведено сравнение с геномными профилями меланом кожи, слизистых оболочек других локализация и увеальными меланомами [23]. Так, были выявлены мутации в генах-драйверах MUC16, RANBP2, NRAS, TP53, PTPRT, NF1, MUC4, KMT2C и BRAF.…”

Section: Discussionunclassified

Endoscopic semiotics and pathological characteristics of primary malignant esophageal melanoma: a case report

Ryabtseva,

Pirogov,

Yutsevich

et al. 2024

ECG

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Primary malignant melanoma of the esophagus is defined as a tumor, the frequency of which is 0.1-0.2% of all malignant lesions of the esophagus. This type of neoplasia is difficult to diagnose and is characterized by rapid progression, high recurrence rate and metastasis. Despite the diagnostic capabilities of X-ray examination methods, which make it possible to identify a tumor and determine its localization, the correct diagnosis can only be established by endoscopic examination of the upper digestive tract with biopsy and subsequent pathological and immunohistochemical studies. A 78 year-old male patient was admitted to the Herzen Moscow State Medical Institute with suspected esophageal cancer. It is known from the anamnesis, that the patient for 6 months notes a dysphagia, pain in the chest area. Based on the data of our expert endoscopic examination, we suspected primary esophageal melanoma with a mixed growth - exophytic and flat-type. According to the results of pathological examination of the biopsies, pigment epithelial-cell melanoma of the esophagus with high mitotic index (up to 3 mitosis figures per 1 sq.mm) with infiltrative growth type. This clinical case demonstrates the importance of a detailed endoscopic examination and performing a targeted biopsy, followed by expert pathological examination in the differential diagnosis of esophageal diseases characterized by pigmentation of mucosa.

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“…For example, MUC16 is one of the most common mutations in patients with cancer of unknown primary (CUP) [ 15 ] and leiomyosarcoma [ 16 ] treated with eribulin and dacarbazine. MUC16 mutations are often detected in Epstein–Barr virus (EBV) associated lymphoepithelioma-like cholangiocarcinoma (EBV-LELCC), which is a rare subtype of intrahepatic cholangiocarcinoma (IHCC) [ 17 ] and in the rare disease primary malignant melanoma of the esophagus (PMME) [ 18 ], suggesting that the patient may be a special type of cancer. There is also a high frequency of MUC16 mutations in Pseudomyxoma peritonei (PMP) of ovarian origin [ 19 ].…”

Section: Muc16 As a Biomarker Of Diseasementioning

confidence: 99%

MUC16: clinical targets with great potential

Zhang,

Hong,

Ling

2024

Clin Exp Med

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Mucin 16 (MUC16) is a membrane-bound mucin that is abnormally expressed or mutated in a variety of diseases, especially tumors, while being expressed in normal body epithelium. MUC16 and its extracellular components are often important cancer-related biomarkers. Abnormal expression of MUC16 promotes tumor progression through mesenchymal protein, PI3K/AKT pathway, JAK2/STAT3 pathway, ERK/FBW7/c-Myc, and other mechanisms, and plays an important role in the occurrence and development of tumors. In addition, MUC16 also helps tumor immune escape by inhibiting T cells and NK cells. Many drugs and trials targeting MUC16 have been developed, and MUC16 may be a new direction for future treatments. In this paper, the mechanism of action of MUC16 in the development of cancer, especially in the immune escape of tumor, is introduced in detail, indicating the potential of MUC16 in clinical treatment.

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Comprehensive genomic analysis of primary malignant melanoma of the esophagus reveals similar genetic patterns compared with epithelium-associated melanomas

Cited by 5 publications

References 40 publications

Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy

Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy

Endoscopic semiotics and pathological characteristics of primary malignant esophageal melanoma: a case report

MUC16: clinical targets with great potential

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