scholarly journals Recurrent differential expression of open reading frames on chromosome 14 in human metastatic breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We leveraged the power of systems-level comparative transcriptome analysis in human tissues to discover genes associated with brain metastasis in human breast cancer by integration of multiple independent published microarray datasets (4-7). We identified five independent open reading frames on chromosome 14 that were among the most differentially expressed, transcriptome-wide, in the brain metastatic tissues of patients with metastatic breast cancer when compared to primary tumors of the breast: C14orf179, C14orf112, C14orf169, C14orf109 and C14orf130. Importantly, primary tumor expression of each of these open reading frames was significantly correlated with either overall, distant metastasis-free, or recurrence-free survival in patients with breast cancer. Analysis of three separate microarray datasets revealed at least five other open reading frames on chromosome 14 that were recurrently transcriptionally modulated in brain metastatic tissues of humans with metastatic breast cancer as evidenced by transcriptome-wide differential expression relative to primary tumors of the breast. It is possible that structural or epigenetic changes on chromosome 14 are a major feature associated with human brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor

In patients with breast cancer, brain metastasis provides limited treatment options (1-3). To discover genes associated with brain metastases in patients with metastatic breast cancer, we mined published microarray datasets, comparing global transcription in brain metastases and primary tumors of the breast (4, 5). Using this methodology, we identified significant differential expression of the G0/G1 switch gene 2, encoded by G0S2, in the brain metastases of patients with breast cancer as compared to primary tumors of the breast. The G0S2 gene product could be of relevance to any one of the numerous processes by which tumor cells in breast cancer metastasize, including exit of the breast, entry into the periphery, breach of the blood brain barrier or colonization of and survival in the brain.


2021 ◽  
Author(s):  
Shahan Mamoor

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 LINC02716, DKFZp779M0652, when comparing primary tumors of the breast to the tissue of origin, the normal breast. DKFZp779M0652 was also differentially expressed in the brain metastases of patients with metastatic breast cancer. DKFZp779M0652 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. DKFZp779M0652 may be of relevance to initiation, maintenance or progression of cancers of the female breast.


2021 ◽  
Author(s):  
Shahan Mamoor

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 for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, 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. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type XVI alpha 1 chain, COL16A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL16A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL16A1 in primary tumors of the breast was correlated with patient overall survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL16A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type VI alpha 1 chain, COL6A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL6A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL6A1 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL6A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that teashirt zinc finger homeobox 3, TSHZ3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSHZ3 was also differentially expressed in brain metastatic tissues. TSHZ3 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSHZ3 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSHZ3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that transmembrane protein 98, TMEM98, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TMEM98 was also differentially expressed in brain metastatic tissues. TMEM98 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TMEM98 in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TMEM98 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

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 for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that the target of myb1-like 2, encoded by TOM1L2, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. TOM1L2 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of TOM1L2 in primary tumors was significantly correlated with patient overall survival in patients with breast cancer. Modulation of TOM1L2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that cluster of differentiation 69, CD69, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that CD69 was also differentially expressed in brain metastatic tissues. CD69 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of CD69 in primary tumors of the breast was correlated with patient overall survival, more significantly in lymph node negative patients than in lymph node positive patients. Modulation of CD69 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

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 for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that diaphanous homolog 2, encoded by DIAPH2, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. DIAPH2 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of DIAPH2 in primary tumors was significantly correlated with patient recurrence-free survival in patients with breast cancer. Modulation of DIAPH2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer. These data are one piece of evidence suggesting a common ancestor or tumor clone for brain and lymph node metastases that originate from the primary tumor, alluding to patterns in developmental origin and migratory pathways through the lymph node in human brain metastatic breast cancer.


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