Detection of homozygous deletions in tumor‐suppressor genes ranging from dozen to hundreds nucleotides in cancer models

2017 ◽  
Vol 38 (11) ◽  
pp. 1449-1453 ◽  
Author(s):  
Lun‐Ching Chang ◽  
Suleyman Vural ◽  
Dmitriy Sonkin
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
Cancer Models ◽  
Homozygous Deletions

scholarly journals Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jorge Muñoz ◽  
María del Mar Inda ◽  
Paula Lázcoz ◽  
Idoya Zazpe ◽  
Xing Fan ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Tumor Suppressor Genes ◽  
Promoter Hypermethylation ◽  
Suppressor Genes ◽  
Primary Tumors ◽  
Specific Pcr ◽  
Inactivation Mechanism ◽  
Altered Gene ◽  
Homozygous Deletions

While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14ARF, and p16INK4A), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14ARF and p16INK4A did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14ARF and p16INK4A, in which other alterations (mutations, homozygous deletions) are prevalent.

scholarly journals Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas

Blood ◽  
2006 ◽  
Vol 109 (1) ◽  
pp. 271-280 ◽  
Author(s):  
Cinta Mestre-Escorihuela ◽  
Fanny Rubio-Moscardo ◽  
Jose A. Richter ◽  
Reiner Siebert ◽  
Joan Climent ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
B Cell ◽  
Tumor Suppressor Genes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Promoter Hypermethylation ◽  
Homozygous Deletion ◽  
Suppressor Genes ◽  
Mantle Cell ◽  
Homozygous Deletions

Abstract Integrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy has identified novel candidate tumor suppressor genes inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes.

Homozygous deletions at 3p22, 5p14, 6q15, and 9p21 result in aberrant expression of tumor suppressor genes in gastric cancer

2014 ◽  
Vol 54 (3) ◽  
pp. 142-155 ◽  
Author(s):  
Bona Lee ◽  
Kwiyeom Yoon ◽  
Sunghoon Lee ◽  
Jin Muk Kang ◽  
Junil Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Aberrant Expression ◽  
Suppressor Genes ◽  
Homozygous Deletions

scholarly journals Candidate tumor-suppressor genes MTS1 (p16INK4A) and MTS2 (p15INK4B) display frequent homozygous deletions in primary cells from T- but not from B-cell lineage acute lymphoblastic leukemias [see comments]

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4038-4044 ◽  
Author(s):  
J Hebert ◽  
JM Cayuela ◽  
J Berkeley ◽  
F Sigaux
Keyword(s):  
Tumor Suppressor ◽  
B Cell ◽  
Tumor Suppressor Gene ◽  
Tumor Suppressor Genes ◽  
Cell Lineage ◽  
Suppressor Gene ◽  
Suppressor Genes ◽  
Multiple Tumor ◽  
B Lineage ◽  
Homozygous Deletions

Using a Southern blot approach, deletions of MTS1 (multiple tumor- suppressor gene 1) and MTS2 (multiple tumor-suppressor gene 2) candidate tumor-suppressor genes have been studied in primary neoplastic cells from 55 acute lymphoblastic leukemia (ALL) patients. Homozygous MTS1 deletions were found in 20 of 24 T-ALL cases and in only 2 of 31 B-lineage cases (P < .001). The deletions involved MTS1 and MTS2 in most cases. Homozygous MTS2 deletions were observed in 16 of 24 T-ALL cases and in 1 of 31 B-lineage ALLs (P < .001), all of them displaying homozygous MTS1 deletions. In 5 cases (4 T and 1 B), deletions involved MTS1 but spared the MTS2 gene, showing that one deletion breakpoint was located between the two genes within a 25-kb region. In 1 T-ALL case, an MTS1 gene rearrangement has occurred downstream to exon 2. Possible hemizygous deletions were found in 6 cases, 4 of them of the B-cell lineage. In 7 ALL cases, cells obtained at presentation and at first relapse were studied and identical results were observed in 6 cases. In 1 B-lineage case, a germline pattern was found at presentation and a possible monoallelic MTS1/MTS2 deletion was observed at relapse. The high frequency of MTS1 and MTS2 homozygous deletions in T-ALLs supports the view that inactivation of these genes plays an important role in the pathogenesis of this type of human leukemia.

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