Genetic analysis of low-grade adenosquamous carcinoma of the breast progressing to high-grade metaplastic carcinoma.

Autor: Kawachi K; Department of Pathology, Kanagawa Cancer Center, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan.; Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, Japan., Tang X; Department of Pathology, Nihon University Hospital, 1-6 Kandasurugadai, Chiyoda-ku, Tokyo, Japan., Kasajima R; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan.; Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan., Yamanaka T; Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan., Shimizu E; Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan., Katayama K; Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan., Yamaguchi R; Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.; Division of Cancer Systems Biology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan.; Division of Cancer Informatics, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-ku, Nagoya, Japan., Yokoyama K; Department of Hematology/Oncology, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Yamaguchi K; Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan., Furukawa Y; Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan., Miyano S; Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.; Department of Integrated Data Science, Medical and Dental Data Science Center, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, Japan., Imoto S; Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan., Yoshioka E; Department of Pathology, Kanagawa Cancer Center, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan., Washimi K; Department of Pathology, Kanagawa Cancer Center, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan., Okubo Y; Department of Pathology, Kanagawa Cancer Center, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan., Sato S; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan., Yokose T; Department of Pathology, Kanagawa Cancer Center, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan., Miyagi Y; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Aasahi-ku, Yokohama, Japan. miyagi@gancen.asahi.yokohama.jp.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2023 Dec; Vol. 202 (3), pp. 563-573. Date of Electronic Publication: 2023 Aug 31.
DOI: 10.1007/s10549-023-07078-9
Abstrakt: Purpose: Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade transformation have been reported; however, the genetics underlying malignant progression of LGASC remain unclear.
Methods: We performed whole-genome sequencing analysis on five MBCs from four patients, including one case with matching primary LGASC and a lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma component (MSC) that progressed from LGASC and three cases of independent de novo MSC.
Results: Unlike de novo MSC, LGASC and its associated MSC showed no TP53 mutation and tended to contain fewer structural variants than de novo MSC. Both LGASC and its associated MSC harbored the common GNAS c.C2530T:p.Arg844Cys mutation, which was more frequently detected in the cancer cell fraction of MSC. MSC associated with LGASC showed additional pathogenic deletions of multiple tumor-suppressor genes, such as KMT2D and BTG1. Copy number analysis revealed potential 18q loss of heterozygosity in both LGASC and associated MSC. The frequency of SMAD4::DCC fusion due to deletions increased with progression to MSC; however, chimeric proteins were not detected. SMAD4 protein expression was already decreased at the LGASC stage due to unknown mechanisms.
Conclusion: Not only LGASC but also its associated high-grade MBC may be genetically different from de novo high-grade MBC. Progression from LGASC to high-grade MBC may involve the concentration of driver mutations caused by clonal selection and inactivation of tumor-suppressor genes.
(© 2023. The Author(s).)
Databáze: MEDLINE
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