Background

Metastatic basal cell carcinoma (mBCC) is a very rare entity, and diagnosis can be challenging. Therapeutic options are limited, and response to targeted therapy is poor.

Objective

To demonstrate a clonal relationship between BCCs and their metastases and to explore which hedgehog pathway-related mutations are involved in mBCC.

Methods

Genetic analysis was conducted in 10 primary BCCs and their metastases. Genes relevant for BCC development were analyzed in tumor and metastasis material with small molecule molecular inversion probes (smMIPs) for PTCH1, PTCH2, SMO, SUFU, GLI2, and TP53 or with targeted next generation sequencing of the same genes and CDKN2A, CDKN2B, CIC, DAXX, DDX3X, FUBP1, NF1, NF2, PTEN, SETD2, TRAF7, and the TERT promoter.

Results

In 8 of 10 patients, identical gene mutations could be demonstrated in the primary tumors and their metastases. A broad spectrum of mutations was found. Four patients had SMO mutations in their tumor or metastasis, or both. All SMO mutations found were known to cause resistance to targeted therapy with vismodegib.

Limitations

In 2 patients there was insufficient qualitative DNA available for genetic analysis.

Conclusions

Molecular testing can help to identify the origin of a BCC metastasis and may be of prognostic and therapeutic value.

中文翻译：

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转移性基底细胞癌的分子检测

背景

转移性基底细胞癌 (mBCC) 是一种非常罕见的疾病，诊断可能具有挑战性。治疗选择有限，对靶向治疗的反应很差。

客观的

证明 BCC 与其转移灶之间的克隆关系，并探索 mBCC 中涉及哪些 Hedgehog 通路相关突变。

方法

对 10 个原发性 BCC 及其转移灶进行遗传分析。使用针对PTCH1、PTCH2、SMO、SUFU、GLI2和TP53的小分子分子倒置探针 (smMIP)或使用相同基因和CDKN2A、CDKN2B、CIC的靶向下一代测序在肿瘤和转移材料中分析与 BCC 发展相关的基因、DAXX、DDX3X、FUBP1、NF1、NF2、PTEN、SETD2、TRAF7和叔启动子。

结果

在 10 名患者中的 8 名中，可以在原发性肿瘤及其转移灶中证实相同的基因突变。发现了广泛的突变。四名患者的肿瘤或转移灶或两者都有SMO突变。已知所有发现的SMO突变都会导致对 vismodegib 靶向治疗产生耐药性。

限制

在 2 名患者中，可用于遗传分析的定性 DNA 不足。

结论

分子检测可以帮助确定 BCC 转移的起源，并可能具有预后和治疗价值。