同一乳腺癌患者多发病灶基因是否相同

　　古希腊哲学家赫拉克利特曾经说过：人不能两次走进同一条河流。意思是说，河里的水是不断流动的，你这次踏进河，水流走了，你下次踏进河时，又流来的是新水，河水川流不息，所以你不能踏进同一条河流。同样，同一河流同一时间不同部位的河水也可能完全不同。不少乳腺癌患者存在多发病灶。对于多发乳腺癌的研究表明，单个病灶内部的生物标志高度一致。不过，同一患者多发病灶的基因是否完全相同？

　　2020年1月13日，英国癌症研究基金会、英国《自然》旗下《英国癌症杂志》在线发表韩国首尔大学医学院、首尔大学盆唐医院的研究报告，探讨了同一乳腺癌患者多发病灶的全部基因是否完全相同。

　　该单中心回顾研究对2009～2012年首尔大学盆唐医院放射学和组织学证实为多发乳腺癌且组织学特征相似的21例患者进行回顾分析。从每位患者选择两个病灶，并对每个病灶的全部生物标志状态进行评估，对170个基因进行目标区域原位杂交捕获法大规模并行测序。

　　结果发现，2例（10%）患者的两个病灶免疫组化亚型不一致：1例患者的两个病灶分别为HER2阳性、三阴性，另1例患者的两个病灶分别为管腔B型HER2高表达、管腔B型HER2低表达。

　　13例患者检测到致病点突变，其中11例患者两个病灶的致癌点突变相同，其余2例患者两个病灶的TP53、ATM、PIK3CA基因点突变结果不同。

　　7例（33%）患者两个病灶的基因拷贝数变化不同，包括2例ERBB2基因、2例FGFR1基因、1例FGFR2基因。

　　因此，该研究结果表明，虽然单个病灶的组织学特征相似，但是超过三分之一患者两个病灶的基因不同，故对多发乳腺癌进行基因检测时，需要考虑多发病灶的基因异质性，不能只见树木、不见森林。

Br J Cancer. 2020 Jan 13. [Epub ahead of print]

Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity.

Soomin Ahn, Hyun Jeong Kim, Eunyoung Kang, Eun-Kyu Kim, Se Hyun Kim, Jee Hyun Kim, In Ah Kim, So Yeon Park.

Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi, Korea.

BACKGROUND: Multiplicity in breast cancer is common. Studies on multiple breast cancers have revealed high concordance in biomarker status among individual lesions. However, genomic differences among multiple lesions are not well-established. We aimed to investigate the potential genomic heterogeneity of multiple breast cancer.

METHODS: Twenty-one patients with radiologically and histologically evident multiple breast cancer with similar histology were included. Two lesions from each of the 21 patients were selected, and biomarker status was evaluated for each lesion. Capture-based targeted next-generation sequencing was performed using a cancer gene panel consisting of 170 genes.

RESULTS: We identified discordance in intrinsic subtype in 2 (10%) of the 21 patients. Pathogenic mutations were detected in 13 of the 21 patients, of whom 11 shared oncogenic variants in the two lesions. The remaining two patients yielded different mutation results for TP53, ATM, and PIK3CA. Difference in copy number alteration was observed in 7 (33%) of the 21 patients including ERBB2 (n=2), FGFR1 (n=2), and FGFR2 (n=1) genes.

CONCLUSION: Despite similar histologic features of the individual lesions, inter-lesional genomic difference was identified in more than one-third of the patients. Inter-lesional genomic heterogeneity needs to be considered when performing a genomic test in multiple breast cancers.

DOI: 10.1038/s41416-019-0713-1