scholarly journals Discordance of PIK3CA and TP53 mutations between breast cancer brain metastases and matched primary tumors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Thulin ◽  
Carola Andersson ◽  
Elisabeth Werner Rönnerman ◽  
Shahin De Lara ◽  
Chaido Chamalidou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Quality Criteria ◽  
Matched Pairs ◽  
Luminal A ◽  
Primary Tumors ◽  
Targeted Next Generation Sequencing ◽  
Mutational Status ◽  
Mutational Pattern ◽  
Breast Cancer Brain Metastases

AbstractThere is limited knowledge of the biology of breast cancer (BC) brain metastasis (BM). We primarily aimed to determine the mutations in BCBM and to compare the mutational pattern with the matched primary breast cancer (BC). Secondary aims were to determine mutations in each subgroup (Luminal A-/B-like, HER2+ and TNBC) of BCBM, and to determine survival according to specific mutations. We investigated 57 BCBMs, including 46 cases with matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. Subtype according to immunohistochemistry was re-evaluated. NGS results fulfilling sequencing quality criteria were obtained from 52 BM and 41 PT, out of which 37 were matched pairs. Pathogenic mutations were detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. We show a discordance of PIK3CA and TP53 mutations of roughly 25% indicating the need to develop methods to assess mutational status in brain metastasis where analysis of cell-free DNA from cerebrospinal fluid (CSF) has shown promising results.

scholarly journals Discordance of PIK3CA and TP53 Mutations Between Breast Cancer Brain Metastases and Matched Primary Tumors

2021 ◽  
Author(s):  
ANNA THULIN ◽  
Carola Andersson ◽  
Elisabeth Rönnerman ◽  
Shahin Lara ◽  
Chaido Chamalidou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Quality Criteria ◽  
Matched Pairs ◽  
Primary Tumors ◽  
Targeted Next Generation Sequencing ◽  
Mutational Status ◽  
Mutational Pattern ◽  
Sequencing Quality ◽  
Breast Cancer Brain Metastases

Abstract Purpose: There is limited knowledge of the biology of breast cancer (BC) brain metastasis (BM). We primarily aimed to determine the mutations in BCBM and to compare the mutational pattern with the matched primary breast cancer (BC). Secondary aims were to determine mutations in each subgroup (Luminal, HER2+ and TNBC) of BCBM and to determine survival according to specific mutations. Patients and methods: We investigated 57 BCBMs, including 46 cases with matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. Subtype according to immunohistochemistry was re-evaluated. Results: NGS results fulfilling sequencing quality criteria were obtained from 52 BM and 41 PT, out of which 37 were matched pairs. Pathogenic mutations were detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. Conclusions: We show a discordance of PIK3CA and TP53 mutations of roughly 25% indicating the need to develop methods to assess mutational status in brain metastasis where analysis of cell-free DNA from cerebrospinal fluid (CSF) has shown promising results.

scholarly journals Discordance of PIK3CA and TP53 Mutations Between Breast Cancer Brain Metastases and Matched Primary Tumors

2021 ◽  
Author(s):  
ANNA THULIN ◽  
Carola Andersson ◽  
Elisabeth Rönnerman ◽  
Shahin De Lara ◽  
Chaido Chamalidou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptors ◽  
Quality Criteria ◽  
Pathogenic Mutation ◽  
Matched Pairs ◽  
Luminal A ◽  
Primary Tumors ◽  
Targeted Next Generation Sequencing ◽  
Sequencing Quality ◽  
Breast Cancer Brain Metastases

Abstract Purpose: Extensive data of mutations in breast cancer (BC) metastases has been published in recent years. However, these studies contain very few patients with brain metastasis (BM). Thus, there is limited knowledge of the biology of BCBM. We primarily aimed to compare the mutational and histological pattern of BM with matched primary breast cancer (BC). Secondary aims were to determine mutations in BMs and PT in each BC subgroup (Luminal, HER2+ and TNBC) and survival according to changed or stable mutations between PTs and BMs. Patients and methods: We investigated 57 BCBMs including 46 cases with the matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. BC subtype according to immunohistochemistry (estrogen- and progesterone receptors, HER2 and Ki67) was obtained by re-evaluation of available tissue from BMs and PT. Results: NGS results fulfilling sequencing quality criteria were obtained from 52 BM (91.2%) and 41 (89.1%) PT, out of which 37 were matched pairs. Pathogenic mutation was detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. Standard BC markers was discordant in 26%, with a loss of the estrogen receptor and a change from Luminal A to other subtypes as the most common. Changes of mutations in BMs compared with PT did not influence survival after diagnose of BM (p=0.4395).Conclusions: We show a discordance of PIK3CA and TP53 mutations, as well as IHC BC subgroups in 25% of the matched pairs of BM and PT, which confirms the need for re-evaluation of mutations, as well as standard BC markers by immunohistochemistry in the BM. Since there are difficulties in obtaining tissue from BM, analysis of cell-free DNA from cerebrospinal fluid (CSF) may be a way forward.

scholarly journals Differential expression of cyclin dependent kinase 5 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Normal Breast ◽  
Cyclin Dependent Kinase ◽  
Luminal A ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Cyclin Dependent Kinase 5

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cyclin dependent kinase 5, CDK5, when comparing primary tumors of the breast to the tissue of origin, the normal breast. CDK5 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of CDK5 in primary tumors of the breast was correlated with distant metastasis-free survival in patients with luminal A subtype cancer. CDK5 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of CKS2 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Regulatory Subunit ◽  
Luminal A ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the CDC28 protein kinase regulatory subunit 2, CKS2, when comparing primary tumors of the breast to the tissue of origin, the normal breast. CKS2 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. CKS2 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of CKS2 in primary tumors of the breast was correlated with overall survival in patients with basal and luminal A subtype cancer, but in a contrary manner. CKS2 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of mab-21 like 1 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Molecular Subtype ◽  
Differentially Expressed Gene ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Luminal A ◽  
Significant Differential Expression ◽  
Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding mab-21 like 1, MAB21L1, when comparing primary tumors of the breast to the tissue of origin, the normal breast. MAB21L1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. MAB21L1 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of MAB21L1 in primary tumors of the breast was correlated with overall survival in patients with luminal A subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by molecular subtype. MAB21L1 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of TUFT1 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Luminal A ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Microarray Datasets

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the tuftelin 1, TUFT1, when comparing primary tumors of the breast to the tissue of origin, the normal breast. TUFT1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. TUFT1 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of TUFT1 in primary tumors of the breast was correlated with distant metastasis-free survival in patients with basal and luminal A subtype cancer. TUFT1 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals The gastrin releasing peptide, GRP, is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Gastrin Releasing Peptide ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the gastrin releasing peptide, encoded by GRP, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Molecular functions of gastrin releasing peptide may be relevant to the processes by which tumor cells of the breast metastasize to the breast. Down-regulation of GRP may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

scholarly journals Differential expression of defective in cullin neddylation 1 domain-containing 3 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Molecular Subtype ◽  
Differentially Expressed Gene ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Luminal A ◽  
Significant Differential Expression ◽  
Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding defective in cullin neddylation 1 domain-containing 3, DCUN1D3, when comparing primary tumors of the breast to the tissue of origin, the normal breast. DCUN1D3 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of DCUN1D3 in primary tumors of the breast was correlated with recurrence-free survival in patients with basal, luminal A and luminal B subtype cancers, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. DCUN1D3 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of KIF11 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Luminal A ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Microarray Datasets

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the kinesin family member 11, KIF11, when comparing primary tumors of the breast to the tissue of origin, the normal breast. KIF11 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. KIF11 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of KIF11 in primary tumors of the breast was correlated with overall survival in patients with basal and luminal A subtype cancer, but in a contrary manner. KIF11 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of dystrophin in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Molecular Subtype ◽  
Differentially Expressed Gene ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Luminal A ◽  
Significant Differential Expression ◽  
Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding dystrophin, DMD, when comparing primary tumors of the breast to the tissue of origin, the normal breast. DMD was also differentially expressed in the tumor cells of patients with triple negative breast cancer. DMD mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of DMD in primary tumors of the breast was correlated with overall survival in patients with basal and luminal A subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by molecular subtype. DMD may be of relevance to initiation, maintenance or progression of cancers of the female breast.

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