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Genomic landscape of extraordinary responses in metastatic breast cancer

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Abstract
Extreme responders to anticancer therapy are rare among advanced breast cancer patients. Researchers, however, have yet to investigate treatment responses therein on the whole exome level. We performed whole exome analysis to characterize the genomic landscape of extreme responders among metastatic breast cancer patients. Clinical samples were obtained from breast cancer patients who showed exceptional responses to anti-HER2 therapy or hormonal therapy and from those who did not. Matched breast tumor tissue (somatic DNA) and blood samples (germline DNA) were collected from a total of 30 responders and 15 non-responders. Whole exome sequencing using Illumina HiSeq2500 was performed for all 45 patients (90 samples). Somatic single nucleotide variants (SNVs), indels, and copy number variants (CNVs) were identified for the genomes of each patient. Group-specific somatic variants and mutational burden were statistically analyzed. Sequencing of cancer exomes for all patients revealed 1839 somatic SNVs (1661 missense, 120 nonsense, 43 splice-site, 15 start/stop-lost) and 368 insertions/deletions (273 frameshift, 95 in-frame), with a median of 0.7 mutations per megabase (range, 0.08 to 4.2 mutations per megabase). Responders harbored a significantly lower nonsynonymous mutational burden (median, 26 vs. 59, P = 0.02) and fewer CNVs (median 13.6 vs. 97.7, P = 0.05) than non-responders. Multivariate analyses of factors influencing progression-free survival showed that a high mutational burden and visceral metastases were significantly related with disease progression. Extreme responders to treatment for metastatic breast cancer are characterized by fewer nonsynonymous mutations and CNVs.

Lim, Kim and Jung et al. report a whole-exome sequence analysis of 30 Korean patients showing extreme treatment responses for metastatic breast cancer. They find that compared to non-responders, extreme responders have fewer nonsynonymous mutations and copy number variants.
Author(s)
구자승권낙정김건민김민환김상우김소라김승일김은영김지예김지형박병우박세호박순명박형석손주혁임선민전민경정경해조영업
Issued Date
2021
Type
Article
Keyword
Breast cancerCancer geneticsCancer genomicsCopy numberDeoxyribonucleic acid--DNAErbB-2 proteinGenomicsMetastasesMetastasisMutationPatientsSequence analysis
DOI
10.1038/s42003-021-01973-x
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8477
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_88ab653ac0f34cc590341be94ab057d0&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Genomic%20landscape%20of%20extraordinary%20responses%20in%20metastatic%20breast%20cancer&offset=0&pcAvailability=true
Publisher
COMMUNICATIONS BIOLOGY
Location
미국
Language
영어
ISSN
2399-3642
Citation Volume
4
Citation Number
1
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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