TY - JOUR
T1 - Genetic variants detected using cell-free DNA from blood and tumor samples in patients with inflammatory breast cancer
AU - Winn, Jennifer S.
AU - Hasse, Zachary
AU - Slifker, Michael
AU - Pei, Jianming
AU - Arisi-Fernandez, Sebastian M.
AU - Talarchek, Jacqueline N.
AU - Obeid, Elias
AU - Baldwin, Donald A.
AU - Gong, Yulan
AU - Ross, Eric
AU - Cristofanilli, Massimo
AU - Alpaugh, R. Katherine
AU - Fernandez, Sandra V.
N1 - Funding Information:
Funding: This work was supported by NIH P30 CA006927 core grant “Comprehensive Cancer Center Program at Fox Chase Cancer Center” and NIH RO1 CA 138239-02 (PI: Cristofanilli).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2/2
Y1 - 2020/2/2
N2 - We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2-IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER-Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in TP53 (47.3%), PMS2 (26.3%), MRE11 (26.3%), RB1 (10.5%), BRCA1 (10.5%), PTEN (10.5%) and AR (10.5%); other affected genes included PMS1, KMT2C, BRCA2, PALB2, MUTYH, MEN1, MSH2, CHEK2, NCOR1, PIK3CA, ESR1 and MAP2K4. In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AFtissue ≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients.
AB - We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2-IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER-Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in TP53 (47.3%), PMS2 (26.3%), MRE11 (26.3%), RB1 (10.5%), BRCA1 (10.5%), PTEN (10.5%) and AR (10.5%); other affected genes included PMS1, KMT2C, BRCA2, PALB2, MUTYH, MEN1, MSH2, CHEK2, NCOR1, PIK3CA, ESR1 and MAP2K4. In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AFtissue ≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients.
KW - Cell-free DNA (cfDNA)
KW - Inflammatory breast cancer (IBC)
KW - Next generation sequencing (NGS)
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U2 - 10.3390/ijms21041290
DO - 10.3390/ijms21041290
M3 - Article
C2 - 32075053
AN - SCOPUS:85079774625
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 4
M1 - 1290
ER -
