PDF(Pubmed)
Abstract：
OBJECTIVE: Compared to primary breast sarcoma (BSs), radiotherapy-induced sarcoma (RIS) is a less frequent type of secondary breast sarcoma. Undifferentiated pleomorphic sarcoma (UPS) is an even rarer occurrence within the RIS category. This study aimed to present the clinicopathologic and molecular features of breast radiotherapy-induced UPS.
METHODS: A retrospective study was conducted at the Third Affiliated Hospital of Soochow University to analyze three patients with radiation-induced undifferentiated pleomorphic sarcoma (UPS) following breast cancer, spanning from 2006 to 2023. The clinical and pathological variables were extracted from the medical records, while immunohistochemistry was employed to analyze the immunophenotypes of these tumors. Genomic characteristics were assessed through DNA and RNA sequencing techniques. Another 15 cases from the literature were also reviewed to better characterize the tumor.
RESULTS: The affected areas encompass the chest wall and breasts, with an incubation period ranging from 6 to 17 years. The tumor cells exhibit pleomorphism and demonstrate a high degree of pathological mitosis. Notably, two cases displayed an accelerated disease progression, characterized by recurrent tumors and metastases occurring within short intervals of 48 and 7 months respectively subsequent to the initial diagnosis. The two prevailing identified genes were TP53 (2/3, 66.7%) and RB1 (1/3, 33.3%). Through analysis of somatic copy number variation (CNV), it was discovered that two oncogenes, MCL1 (1/3, 33.3%) and MYC (1/3, 33.3%), had experienced gains in CNV. The Tumor Mutational Burden (TMB) values for case 1, case 2, and case 3 were 5.9 mut/Mb, 1.0 mut/Mb, and 3.0 mut/Mb, respectively. Moreover, the analysis of RNA-NGS (next-generation sequencing) revealed the presence of a novel gene fusion, named COL3A1-GULP1, in case 2.
CONCLUSIONS: Based on our thorough analysis of research findings and previous reports, it is evident that radiotherapy-induced UPS exhibits a highly diverse and frequently severe clinical and biological behavior. Identifying tumor formation using genome sequencing can help understand its biological behavior and determine personalized treatments.
METHODS: A retrospective study was conducted at the Third Affiliated Hospital of Soochow University to analyze three patients with radiation-induced undifferentiated pleomorphic sarcoma (UPS) following breast cancer, spanning from 2006 to 2023. The clinical and pathological variables were extracted from the medical records, while immunohistochemistry was employed to analyze the immunophenotypes of these tumors. Genomic characteristics were assessed through DNA and RNA sequencing techniques. Another 15 cases from the literature were also reviewed to better characterize the tumor.
RESULTS: The affected areas encompass the chest wall and breasts, with an incubation period ranging from 6 to 17 years. The tumor cells exhibit pleomorphism and demonstrate a high degree of pathological mitosis. Notably, two cases displayed an accelerated disease progression, characterized by recurrent tumors and metastases occurring within short intervals of 48 and 7 months respectively subsequent to the initial diagnosis. The two prevailing identified genes were TP53 (2/3, 66.7%) and RB1 (1/3, 33.3%). Through analysis of somatic copy number variation (CNV), it was discovered that two oncogenes, MCL1 (1/3, 33.3%) and MYC (1/3, 33.3%), had experienced gains in CNV. The Tumor Mutational Burden (TMB) values for case 1, case 2, and case 3 were 5.9 mut/Mb, 1.0 mut/Mb, and 3.0 mut/Mb, respectively. Moreover, the analysis of RNA-NGS (next-generation sequencing) revealed the presence of a novel gene fusion, named COL3A1-GULP1, in case 2.
CONCLUSIONS: Based on our thorough analysis of research findings and previous reports, it is evident that radiotherapy-induced UPS exhibits a highly diverse and frequently severe clinical and biological behavior. Identifying tumor formation using genome sequencing can help understand its biological behavior and determine personalized treatments.
摘要：
目的：与原发性乳腺肉瘤（BS）相比，放疗诱导的肉瘤（RIS）是一种不太常见的继发性乳腺肉瘤。未分化多形性肉瘤（UPS）在RIS类别中更为罕见。本研究旨在介绍乳腺放疗诱导UPS的临床病理和分子特征。
方法：苏州大学附属第三医院进行回顾性研究，分析3例乳腺癌后放射性未分化多形性肉瘤（UPS）患者，从2006年到2023年。从病历中提取临床和病理变量，而免疫组织化学用于分析这些肿瘤的免疫表型。通过DNA和RNA测序技术评估基因组特征。还回顾了文献中的另外15例病例，以更好地表征肿瘤。
结果：受影响的区域包括胸壁和乳房，潜伏期从6年到17年不等。肿瘤细胞表现出多态性，并表现出高度的病理性有丝分裂。值得注意的是,两个病例显示疾病进展加速，以最初诊断后分别在48个月和7个月内发生的复发肿瘤和转移为特征。两个主要的鉴定基因是TP53（2/3，66.7％）和RB1（1/3，33.3％）。通过分析体细胞拷贝数变异（CNV），发现了两个癌基因，MCL1（1/3，33.3%）和MYC（1/3，33.3%），经历了CNV的增长。病例1、病例2和病例3的肿瘤突变负担(TMB)值为5.9mut/Mb,1.0mut/Mb，和3.0mut/Mb，分别。此外，RNA-NGS（下一代测序）的分析揭示了一种新的基因融合的存在，命名为COL3A1-GULP1，在情况2。
结论：根据我们对研究结果和以前报告的全面分析，很明显,放射疗法诱导的UPS表现出高度多样且经常严重的临床和生物学行为。使用基因组测序识别肿瘤形成可以帮助了解其生物学行为并确定个性化治疗。
方法：苏州大学附属第三医院进行回顾性研究，分析3例乳腺癌后放射性未分化多形性肉瘤（UPS）患者，从2006年到2023年。从病历中提取临床和病理变量，而免疫组织化学用于分析这些肿瘤的免疫表型。通过DNA和RNA测序技术评估基因组特征。还回顾了文献中的另外15例病例，以更好地表征肿瘤。
结果：受影响的区域包括胸壁和乳房，潜伏期从6年到17年不等。肿瘤细胞表现出多态性，并表现出高度的病理性有丝分裂。值得注意的是,两个病例显示疾病进展加速，以最初诊断后分别在48个月和7个月内发生的复发肿瘤和转移为特征。两个主要的鉴定基因是TP53（2/3，66.7％）和RB1（1/3，33.3％）。通过分析体细胞拷贝数变异（CNV），发现了两个癌基因，MCL1（1/3，33.3%）和MYC（1/3，33.3%），经历了CNV的增长。病例1、病例2和病例3的肿瘤突变负担(TMB)值为5.9mut/Mb,1.0mut/Mb，和3.0mut/Mb，分别。此外，RNA-NGS（下一代测序）的分析揭示了一种新的基因融合的存在，命名为COL3A1-GULP1，在情况2。
结论：根据我们对研究结果和以前报告的全面分析，很明显,放射疗法诱导的UPS表现出高度多样且经常严重的临床和生物学行为。使用基因组测序识别肿瘤形成可以帮助了解其生物学行为并确定个性化治疗。
