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Genetic heterogeneity during breast cancer progression in young patients

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Title: Genetic heterogeneity during breast cancer progression in young patients
Authors: Hagio, Kanako Browse this author
Hatanaka, Kanako C. Browse this author
Amano, Toraji Browse this author
Matsuno, Yoshihiro Browse this author
Hatanaka, Yutaka Browse this author →KAKEN DB
Yamashita, Hiroko Browse this author →KAKEN DB
Keywords: Breast cancer
Ductal carcinoma in situ
Invasive carcinoma
Heterogeneity
Targeted sequencing
Young women
Issue Date: Dec-2021
Publisher: Elsevier
Journal Title: Breast
Volume: 60
Start Page: 206
End Page: 213
Publisher DOI: 10.1016/j.breast.2021.10.011
Abstract: Background: Because a number of years may be required for normal cells to develop into carcinoma, genes involved in tumorigenesis and progression might differ among breast cancers in young women and those in older women. The present study sought to analyze subclonality during breast cancer evolution as well as diversity within each individual in our young patients' cohort. Methods: A total of 13 women aged <35 years at diagnosis with early breast cancer were recruited. Serial sections of breast samples consisting of synchronous invasive carcinoma, adjacent ductal carcinoma in situ (DCIS), normal breast tissue, and metastatic lymph nodes were collected and prepared for immunohistochemical analysis of estrogen receptor, progesterone receptor, HER2, and Ki67, and for extraction of genomic DNA. Germline and somatic gene alterations of genomic DNA were examined by targeted sequencing. Results: Genomic DNA from 13 blood samples and 36 breast tissues consisting of 14 invasive carcinomas, nine adjacent DCIS, 11 normal breast tissues, and two metastatic lymph nodes were successfully sequenced. Germline gene alterations including pathogenic variants and gene alterations that were not yet evaluated for their clinical significance were detected in all patients but one. Somatic gene alterations were identified in eight invasive carcinomas, five DCIS, and one metastatic lymph node. Different somatic gene alterations between invasive carcinoma and DCIS were detected in two patients. Somatic gene mutations were present in non-neoplastic tissues in three patients. No two patients had the same gene alterations. Conclusion: Our results reveal diversity within each individual during breast cancer progression. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Type: article
URI: http://hdl.handle.net/2115/84262
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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