Germline and somatic NF1 alterations are linked to increased HER2 expression in breast cancer

Xia Wang, Roope A. Kallionpaa, Patrick R. Gonzales, Dhananjay A. Chitale, Renee N. Tousignant, Jacob P. Crowley, Zhihua Chen, Sean J. Yoder, Jaishri Blakeley, Maria T. Acosta, Bruce R. Korf, Ludwine M. Messiaen, Michael A. Tainsky

Research output: Contribution to journalArticle

Abstract

NF1 germline mutation predisposes to breast cancer. NF1 mutations have also been proposed as oncogenic drivers in sporadic breast cancers. To understand the genomic and histologic characteristics of these breast cancers, we analyzed the tumors with NF1 germline mutations and also examined the genomic and proteomic profiles of unselected tumors. Among 14 breast cancer specimens from 13 women affected with neuro-fibromatosis type 1 (NF1), 9 samples (NF þ BrCa) underwent genomic copy number (CN) and targeted sequencing analysis. Mutations of NF1 were identified in two samples and TP53 were in three. No mutation was detected in ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, and STK11. HER2 (ErbB2) overexpression was detected by IHC in 69.2% (9/13) of the tumors. CN gain/amplification of ERBB2 was detected in 4 of 9 with DNA analysis. By evaluating HER2 expression and NF1 alterations in unselected invasive breast cancers in TCGA datasets, we discovered that among samples with ERBB2 CN gain/amplification, the HER2 mRNA and protein expression were much more pronounced in NF1-mutated/deleted samples in comparison with NF1-unaltered samples. This finding suggests a synergistic interplay between these two genes, potentially driving the development of breast cancer harboring NF1 mutation and ERBB2 CN gain/amplification. NF1 gene loss of heterozygosity was observed in 4 of 9 NF þ BrCa samples. CDK4 appeared to have more CN gain in NF þ BrCa and exhibited increased mRNA expression in TCGA NF1-altered samples.

Original languageEnglish (US)
Pages (from-to)655-663
Number of pages9
JournalCancer Prevention Research
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Fibroma
Breast Neoplasms
Mutation
Germ-Line Mutation
Neoplasms
Messenger RNA
Loss of Heterozygosity
Proteomics
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wang, X., Kallionpaa, R. A., Gonzales, P. R., Chitale, D. A., Tousignant, R. N., Crowley, J. P., ... Tainsky, M. A. (2018). Germline and somatic NF1 alterations are linked to increased HER2 expression in breast cancer. Cancer Prevention Research, 11(10), 655-663. https://doi.org/10.1158/1940-6207.CAPR-18-0072

Germline and somatic NF1 alterations are linked to increased HER2 expression in breast cancer. / Wang, Xia; Kallionpaa, Roope A.; Gonzales, Patrick R.; Chitale, Dhananjay A.; Tousignant, Renee N.; Crowley, Jacob P.; Chen, Zhihua; Yoder, Sean J.; Blakeley, Jaishri; Acosta, Maria T.; Korf, Bruce R.; Messiaen, Ludwine M.; Tainsky, Michael A.

In: Cancer Prevention Research, Vol. 11, No. 10, 01.10.2018, p. 655-663.

Research output: Contribution to journalArticle

Wang, X, Kallionpaa, RA, Gonzales, PR, Chitale, DA, Tousignant, RN, Crowley, JP, Chen, Z, Yoder, SJ, Blakeley, J, Acosta, MT, Korf, BR, Messiaen, LM & Tainsky, MA 2018, 'Germline and somatic NF1 alterations are linked to increased HER2 expression in breast cancer', Cancer Prevention Research, vol. 11, no. 10, pp. 655-663. https://doi.org/10.1158/1940-6207.CAPR-18-0072
Wang X, Kallionpaa RA, Gonzales PR, Chitale DA, Tousignant RN, Crowley JP et al. Germline and somatic NF1 alterations are linked to increased HER2 expression in breast cancer. Cancer Prevention Research. 2018 Oct 1;11(10):655-663. https://doi.org/10.1158/1940-6207.CAPR-18-0072
Wang, Xia ; Kallionpaa, Roope A. ; Gonzales, Patrick R. ; Chitale, Dhananjay A. ; Tousignant, Renee N. ; Crowley, Jacob P. ; Chen, Zhihua ; Yoder, Sean J. ; Blakeley, Jaishri ; Acosta, Maria T. ; Korf, Bruce R. ; Messiaen, Ludwine M. ; Tainsky, Michael A. / Germline and somatic NF1 alterations are linked to increased HER2 expression in breast cancer. In: Cancer Prevention Research. 2018 ; Vol. 11, No. 10. pp. 655-663.
@article{b718b0d553dc407cb1cdd4d96dd4e1bb,
title = "Germline and somatic NF1 alterations are linked to increased HER2 expression in breast cancer",
abstract = "NF1 germline mutation predisposes to breast cancer. NF1 mutations have also been proposed as oncogenic drivers in sporadic breast cancers. To understand the genomic and histologic characteristics of these breast cancers, we analyzed the tumors with NF1 germline mutations and also examined the genomic and proteomic profiles of unselected tumors. Among 14 breast cancer specimens from 13 women affected with neuro-fibromatosis type 1 (NF1), 9 samples (NF {\th} BrCa) underwent genomic copy number (CN) and targeted sequencing analysis. Mutations of NF1 were identified in two samples and TP53 were in three. No mutation was detected in ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, and STK11. HER2 (ErbB2) overexpression was detected by IHC in 69.2{\%} (9/13) of the tumors. CN gain/amplification of ERBB2 was detected in 4 of 9 with DNA analysis. By evaluating HER2 expression and NF1 alterations in unselected invasive breast cancers in TCGA datasets, we discovered that among samples with ERBB2 CN gain/amplification, the HER2 mRNA and protein expression were much more pronounced in NF1-mutated/deleted samples in comparison with NF1-unaltered samples. This finding suggests a synergistic interplay between these two genes, potentially driving the development of breast cancer harboring NF1 mutation and ERBB2 CN gain/amplification. NF1 gene loss of heterozygosity was observed in 4 of 9 NF {\th} BrCa samples. CDK4 appeared to have more CN gain in NF {\th} BrCa and exhibited increased mRNA expression in TCGA NF1-altered samples.",
author = "Xia Wang and Kallionpaa, {Roope A.} and Gonzales, {Patrick R.} and Chitale, {Dhananjay A.} and Tousignant, {Renee N.} and Crowley, {Jacob P.} and Zhihua Chen and Yoder, {Sean J.} and Jaishri Blakeley and Acosta, {Maria T.} and Korf, {Bruce R.} and Messiaen, {Ludwine M.} and Tainsky, {Michael A.}",
year = "2018",
month = "10",
day = "1",
doi = "10.1158/1940-6207.CAPR-18-0072",
language = "English (US)",
volume = "11",
pages = "655--663",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Germline and somatic NF1 alterations are linked to increased HER2 expression in breast cancer

AU - Wang, Xia

AU - Kallionpaa, Roope A.

AU - Gonzales, Patrick R.

AU - Chitale, Dhananjay A.

AU - Tousignant, Renee N.

AU - Crowley, Jacob P.

AU - Chen, Zhihua

AU - Yoder, Sean J.

AU - Blakeley, Jaishri

AU - Acosta, Maria T.

AU - Korf, Bruce R.

AU - Messiaen, Ludwine M.

AU - Tainsky, Michael A.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - NF1 germline mutation predisposes to breast cancer. NF1 mutations have also been proposed as oncogenic drivers in sporadic breast cancers. To understand the genomic and histologic characteristics of these breast cancers, we analyzed the tumors with NF1 germline mutations and also examined the genomic and proteomic profiles of unselected tumors. Among 14 breast cancer specimens from 13 women affected with neuro-fibromatosis type 1 (NF1), 9 samples (NF þ BrCa) underwent genomic copy number (CN) and targeted sequencing analysis. Mutations of NF1 were identified in two samples and TP53 were in three. No mutation was detected in ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, and STK11. HER2 (ErbB2) overexpression was detected by IHC in 69.2% (9/13) of the tumors. CN gain/amplification of ERBB2 was detected in 4 of 9 with DNA analysis. By evaluating HER2 expression and NF1 alterations in unselected invasive breast cancers in TCGA datasets, we discovered that among samples with ERBB2 CN gain/amplification, the HER2 mRNA and protein expression were much more pronounced in NF1-mutated/deleted samples in comparison with NF1-unaltered samples. This finding suggests a synergistic interplay between these two genes, potentially driving the development of breast cancer harboring NF1 mutation and ERBB2 CN gain/amplification. NF1 gene loss of heterozygosity was observed in 4 of 9 NF þ BrCa samples. CDK4 appeared to have more CN gain in NF þ BrCa and exhibited increased mRNA expression in TCGA NF1-altered samples.

AB - NF1 germline mutation predisposes to breast cancer. NF1 mutations have also been proposed as oncogenic drivers in sporadic breast cancers. To understand the genomic and histologic characteristics of these breast cancers, we analyzed the tumors with NF1 germline mutations and also examined the genomic and proteomic profiles of unselected tumors. Among 14 breast cancer specimens from 13 women affected with neuro-fibromatosis type 1 (NF1), 9 samples (NF þ BrCa) underwent genomic copy number (CN) and targeted sequencing analysis. Mutations of NF1 were identified in two samples and TP53 were in three. No mutation was detected in ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, and STK11. HER2 (ErbB2) overexpression was detected by IHC in 69.2% (9/13) of the tumors. CN gain/amplification of ERBB2 was detected in 4 of 9 with DNA analysis. By evaluating HER2 expression and NF1 alterations in unselected invasive breast cancers in TCGA datasets, we discovered that among samples with ERBB2 CN gain/amplification, the HER2 mRNA and protein expression were much more pronounced in NF1-mutated/deleted samples in comparison with NF1-unaltered samples. This finding suggests a synergistic interplay between these two genes, potentially driving the development of breast cancer harboring NF1 mutation and ERBB2 CN gain/amplification. NF1 gene loss of heterozygosity was observed in 4 of 9 NF þ BrCa samples. CDK4 appeared to have more CN gain in NF þ BrCa and exhibited increased mRNA expression in TCGA NF1-altered samples.

UR - http://www.scopus.com/inward/record.url?scp=85054347822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054347822&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-18-0072

DO - 10.1158/1940-6207.CAPR-18-0072

M3 - Article

C2 - 30104415

AN - SCOPUS:85054347822

VL - 11

SP - 655

EP - 663

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 10

ER -