上世紀，乳腺癌被簡單分為激素受體陽性、激素受體陰性。2000年，全球自然科學三大旗艦期刊之首、英國《自然》正刊發(fā)表美國斯坦福大學博士后查爾斯·佩魯?shù)葘W者的研究報告，分析了42例乳腺癌患者化療前后65份腫瘤和淋巴結(jié)的8102種基因表達，根據(jù)激素受體、人類表皮生長因子受體HER2、增殖指數(shù)Ki67，首次提出了乳腺癌的分子分型：管腔型（激素受體陽性）、基底型（激素受體陰性且HER2陰性）、HER2過表達型（激素受體陰性且HER2陽性），對指導乳腺癌分型治療起到了巨大作用。不過，該分子分型主要適用于導管浸潤癌，其他少見組織學分型乳腺癌仍然缺乏明確的分子分型。同年，查爾斯·佩魯也完成了博士后研究工作，前往北卡羅來納大學工作至今。
2021年12月8日，美國《細胞》旗下《細胞基因組學》在線發(fā)表北卡羅來納大學查爾斯·佩魯團隊、斯坦福大學、哈佛大學、貝斯以色列醫(yī)院和新英格蘭女執(zhí)事醫(yī)院、布萊根醫(yī)院和波士頓婦女醫(yī)院、達納法伯癌癥研究所、波士頓病理學人工智能、舊金山加利福尼亞大學、中國香港中文大學威爾斯親王醫(yī)院的研究報告，借助美國國家癌癥研究所（NCI）和國家人類基因組研究所（NHGRI）癌癥基因組圖譜（TCGA）乳腺癌數(shù)據(jù)集，進一步對不同組織學分型乳腺癌進行了分子分型。查爾斯·佩魯已由21年前的第一作者轉(zhuǎn)為通信作者。
該研究首先對癌癥基因組圖譜乳腺癌數(shù)據(jù)集共計1095例乳腺癌的原發(fā)腫瘤標本進行組織學分型，其中導管浸潤癌647例、小葉浸潤癌183例、特殊組織學分型癌99例、混合組織學分型癌129例、無法分型37例。隨后，通過分析該擴展數(shù)據(jù)集，確定了六種少見的特殊組織學分型乳腺癌（篩狀癌、微乳頭狀癌、黏液癌、乳頭狀癌、化生癌、髓樣浸潤癌）轉(zhuǎn)錄組和基因組特征，包括分化評分、分子分型、增殖指數(shù)、基因拷貝數(shù)量、P53基因突變、免疫特征。該特殊組織學分型基因特征還可廣泛適用于癌癥基因組圖譜全部癌癥數(shù)據(jù)集，其預測模型可檢出其他器官系統(tǒng)癌癥的黏液組織學分型。利用正常乳腺細胞分化評分分析，可將組織學分型從干細胞樣到管腔祖細胞樣到成熟管腔樣進行連續(xù)排序。最后，根據(jù)基因組特征＋組織學特征，可將癌癥基因組圖譜乳腺癌數(shù)據(jù)集分為12組具有共同生物特征的乳腺癌：導管浸潤癌基底型、導管浸潤癌管腔A型、導管浸潤癌管腔B型、導管浸潤癌HER2過表達型、小葉浸潤癌管腔型、篩狀癌、微乳頭狀癌、乳頭狀癌管腔型、化生癌密封蛋白低表達型、化生癌、黏液癌、髓樣癌。
因此，該研究結(jié)果大大擴展了癌癥基因組圖譜乳腺癌數(shù)據(jù)集的基因組、分子和組織學特征，為不同組織學類型乳腺癌的深入研究和精準治療奠定了基礎(chǔ)。
相關(guān)鏈接
Cell Genom. 2021 Dec 8;1(3):100067.
Molecular analysis of TCGA breast cancer histologic types.
Aatish Thennavan, Francisco Beca, Youli Xia, Susana Garcia-Recio, Kimberly Allison, Laura C. Collins, Gary M. Tse, Yunn-Yi Chen, Stuart J. Schnitt, Katherine A. Hoadley, Andrew Beck, Charles M. Perou.
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Stanford University School of Medicine, Stanford, CA, USA; Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; University of California, San Francisco, San Francisco, CA, USA; Brigham and Women's Hospital and Harvard Medical School, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA; PathAI, Boston, MA, USA; Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Highlights
The complete histologic annotation for all 1,095 TCGA primary breast cancer patient samples
Genomic and molecular signatures of six rare breast cancer histologic types
Utility of constructed mucinous gene signature in pan-cancer mucinous cancers
Genomic- and histology-integrated model classifies 12 consensus groups
Breast cancer is classified into multiple distinct histologic types, and many of the rarer types have limited characterization. Here, we extend The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset with additional histologic type annotations in a total of 1,063 breast cancers. We analyze this extended dataset to define transcriptomic and genomic profiles of six rare, special histologic types: cribriform, micropapillary, mucinous, papillary, metaplastic, and invasive carcinoma with medullary pattern. We show the broader applicability of our constructed special histologic type gene signatures in the TCGA Pan-Cancer Atlas dataset with a predictive model that detects mucinous histologic type across cancers of other organ systems. Using a normal mammary cell differentiation score analysis, we order histologic types into a continuum from stem cell-like to luminal progenitor-like to mature luminal-like. Finally, we classify TCGA-BRCA into 12 consensus groups based on integrated genomic and histological features. We present a rich, openly accessible resource of genomic, molecular, and histologic characterization of TCGA-BRCA to enable studies across the range of breast cancers.
KEYWORDS: breast cancer; histologic type; PAM50; molecular subtype; claudin-low; mucinous; papillary; metaplastic
DOI: 10.1016/j.xgen.2021.100067
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