0 90

Cited 0 times in

Genomic Alterations during the In Situ to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System

Authors
 Anne Trinh  ;  Carlos R Gil Del Alcazar  ;  Sachet A Shukla  ;  Koei Chin  ;  Young Hwan Chang  ;  Guillaume Thibault  ;  Jennifer Eng  ;  Bojana Jovanović  ;  C Marcelo Aldaz  ;  So Yeon Park  ;  Joon Jeong  ;  Catherine Wu  ;  Joe Gray  ;  Kornelia Polyak 
Citation
 MOLECULAR CANCER RESEARCH, Vol.19(4) : 623-635, 2021-04 
Journal Title
MOLECULAR CANCER RESEARCH
ISSN
 1541-7786 
Issue Date
2021-04
Abstract
The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions. Immune "hot" and "cold" tumors can arise as early as DCIS and are subtype-specific. Topologic analysis showed a similar degree of pan-leukocyte-tumor mixing in both DCIS and IDC but differ when assessing specific immune subpopulations such as CD4 T cells and CD68 macrophages. Tumor-specific copy-number aberrations in MHC-I presentation machinery and losses in 3p, 4q, and 5p are associated with differences in immune signaling in estrogen receptor (ER)-negative IDC. Common oncogenic hotspot mutations in genes including TP53 and PIK3CA are predicted to be neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition, and are associated with differences in immune signaling. We highlight both tumor and immune-specific changes in the transition of pure DCIS to IDC, including genetic changes in tumor cells that may have a role in modulating immune function and assist in immune escape, driving the transition to IDC. IMPLICATIONS: We demonstrate that the in situ to IDC evolutionary bottleneck is shaped by both tumor and immune cells.
Full Text
https://mcr.aacrjournals.org/content/19/4/623.long
DOI
10.1158/1541-7786.MCR-20-0949
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Jeong, Joon(정준) ORCID logo https://orcid.org/0000-0003-0397-0005
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184242
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links