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 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 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 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.

Distribution of Estrogen and Progesterone Receptors in Primary Tumor and Lymph Nodes in Individual Patients with Breast Cancer

1984 ◽  
Vol 70 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Danila Coradini ◽  
Vera Cappelletti ◽  
Patrizia Miodini ◽  
Enrico Ronchi ◽  
Gianfranco Scavone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Progesterone Receptors ◽  
Cancer Tissue ◽  
Primary Tumors ◽  
Er Positive ◽  
Malignant Lymph Nodes ◽  
Negative Lymph Nodes ◽  
Primary Breast Cancer Tissue

Primary breast cancer tissue and lymph nodes were obtained from 48 patients. Estrogen receptors (ER) and progesterone receptors (PgR) were determined by a dextran-coated charcoal assay. ER were present in 72.9 % of the primary tumors and in 62.4 % of the malignant lymph nodes, whereas PgR were present in 73.0 % and 50.0 % of the cases, respectively. The primary tumor and the corresponding malignant lymph nodes showed an identical ER and PgR status, i.e., both tumor sites were receptor positive or both receptor negative in 89.6 % and 77.1 %, respectively. However, 10.4 % of the patients had ER-positive tumors but ER-negative lymph nodes and 22.9 % had PgR-positive primaries with PgR-negative lymph nodes. No receptor-positive lymph nodes showed a combination with receptor-negative primary tumor. This preliminary data shows that receptor-positive malignant lymph nodes mostly display the same receptor status as the corresponding primary tumor, whereas receptor-negative lymph nodes may have a receptor-positive primary tumor.

Sign in / Sign up

Export Citation Format

Share Document