Transcript Map of the 8p23 Putative Tumor Suppressor Region

Sun, Paul C.; Uppaluri, Ravindra; Schmidt, Amy P.; Pashia, Mary E.; Quant, E. C.; Sunwoo, John B.; Gollin, Susanne M.; Scholnick, Steven B.

doi:10.1006/geno.2001.6587

Cited by 86 publications

(90 citation statements)

References 33 publications

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“…Through the use of RT-PCR methods and expressed sequence tags (ESTs), Sun et al 16 identified the CSMD1 gene (CUB and sushi multiple domains-1) as a putative TSG at 8p23. At 8p23.2, the CSMD1 gene spans from 2.78 cM to 4.84 cm from the p-terminus and encodes a transmembrane protein of unknown function.…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of loss of heterozygosity at 8p21 and 9p21 in head and neck squamous cell carcinoma

Coon

Savera

Zarbo

et al. 2004

Intl Journal of Cancer

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Loss of heterozygosity (LOH) in chromosomal regions that harbor tumor suppressor genes from tumor tissue may lead to decreased survival time in cancer patients with squamous cell carcinoma of the head and neck (HNSCC). We studied 8 regions frequently lost in HNSCC in 150 patients having a primary diagnosis of HNSCC. Tumor and normal tissue DNA were genotyped for microsatellite repeat markers in 8 unlinked chromosomal regions. The association between LOH and death from HNSCC was investigated, weighted by number of informative markers per region and adjusted for age at diagnosis, self-reported race, tumor stage and current smoking status. LOH at 3 chromosomal regions were independently associated with reduced survival. A greater risk for cancer mortality was observed for LOH at chromosomal regions 3p24. Cure rates for patients with squamous cell carcinoma of the head and neck (HNSCC) are low. According to Surveillance, Epidemiology and End Results (SEER) data, the 5-year survival rate for cancers of the larynx is 65.9% and for cancers of the oral cavity and pharynx only 58.8%. 1 Few reliable postdiagnosis prognostic indicators exist. TNM tumor staging, which incorporates information regarding the size of the tumor (T) as well as descriptions of the regional nodes (N) and distant metastases (M), is the most common clinical method for assessing prognosis and aides the clinician in the selection of an appropriate treatment regimen for the individual patient. 2 To illustrate, SEER 5-year survival rates decrease from 81.9% for localized to 46.7% for regional and 23.4% for distant metastatic tumors of the pharynx and oral cavity with a similar trend seen in laryngeal tumors: 82.0%, 51.0% and 37.7%, respectively. 1 Although SEER data demonstrate the strong correlation between tumor stage and survival, there is much variation in outcome within each tumor stage that remains unresolved.Other established clinical factors that contribute to the treatment decision-making process include tumor site, pathologic grading of differentiation, performance status and overall treatment time. 3,4 Nevertheless, such indicators alone do not adequately predict outcome. Additional patient-specific prognostic indicators, such as genetic biomarkers, are needed to allow the physician to better identify those who are most likely to benefit from aggressive therapy. 5 Loss of heterozygosity (LOH) at specific markers may offer additional prognostic information to aid in the selection of an appropriate treatment course.Numerous genetic changes accumulate in HNSCC tumors, but the relative importance of specific genetic sites to patient survival remains uncertain. Our previous work had shown a high frequency of cytogenetic abnormalities, most commonly visible chromosomal deletions, at the following 8 chromosomal regions: 3p14. 2-p13, 3p24.3-p14.3, 5q11.2-q31.3, 8p21.3-11.21, 9p21-p24, 10p12.1-p11.22, 18q12.3-q23 and 21q21.1-q22.2. 6 We continue this work by examining allelic loss at the molecular level. Several of these regions have been supported ...

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Section: Discussionmentioning

confidence: 99%

Prognostic implications of loss of heterozygosity at 8p21 and 9p21 in head and neck squamous cell carcinoma

Coon

Savera

Zarbo

et al. 2004

Intl Journal of Cancer

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“…A candidate tumorsuppressor gene in 8p23 has been reported. 34 Furthermore, alterations in chromosome 8 are enough to generate intercellular variability leading to different cell populations, e.g., the KM12C cell line. Chromosome 12 is also frequently involved in translocations, and the short arm is often deleted.…”

Section: Discussionmentioning

confidence: 99%

Genetic evolution in colon cancer KM12 cells and metastatic derivates

Camps

Morales

Prat

et al. 2004

Intl Journal of Cancer

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So far, CRC cell lines have contributed to descriptions of 2 patterns of genetic instability, affecting either microsatellite sequences or chromosome number and structure. Often, these patterns are mutually exclusive; while near-diploid karyotypes usually appear with MSI and chromosomal stability, near-triploid or tetraploid cells display a high degree of CIN and are stable at the microsatellite level. In the present study, we describe the genomic instability pattern of KM12 CRC cells. KM12C and derived cell lines with different metastatic properties were analyzed by conventional cytogenetics, CGH and M-FISH. Results were compared to 5 cell lines usually used as model of MSI and CIN. Concordance between our results and previously published SKY data are also reviewed. Interestingly, the poorly metastatic KM12C cell line displayed a near-diploid karyotype with high levels of structural chromosome instability and microsatellite instability. Most carcinomas show highly complex karyotypes, suggesting that one of the tumor-development events may be related to genomic instability. 1,2 Up to now, MSI has been the only type of genomic instability well characterized in a minority of tumors (about 15% of sporadic CRCs). These tumors show a deficiency in mismatch repair genes with a replication error phenotype and a stable near-diploid karyotype. 3-7 chromosome instability has been described in some CRC cell lines, resulting in numerical changes 8 (CIN) or structural rearrangements. 9 Often, these patterns are mutually exclusive; while near-diploid karyotypes usually appear with MSI and chromosome instability, near-triploid or tetraploid cells display a high degree of CIN and are stable at the microsatellite level.It has been postulated that primary alterations in solid tumors consist of submicroscopic mutations, whereas unbalanced chromosomal rearrangements, whether numerical or structural, are secondary events and most likely associated with selective pressures during tumor progression. 10 A previous report demonstrated clonal chromosomal aberrations in 87% of CRC tumors analyzed. 11 The most frequent numerical changes were, in order of decreasing frequency, ϩ7, -18, -14, ϩ13. Gain of chromosome 8q and loss of 8p, loss of 17p and gain of 17q as well as loss of the entire chromosome 22 are also unbalanced rearrangements that have been reported. 11 Based on cytogenetic alterations, Dutrillaux 12 proposed 3 different evolutionary pathways: monosomic-type tumors undergo structural rearrangements resulting in gains and losses of different chromosome arms and show a relatively high rate of endoreduplication, leading to the formation of hypotetraploid clones that evolve to near-triploid cells; trisomic cells are characterized by tumors with a progressive increase in chromosome number but accompanied by a scarce number of rearrangements; tumors that display a near-normal karyotype and MSI were grouped into the normal type. Unbalanced chromosomal abnormalities would be secondary events and most likely associated with selective pre...

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“…CSMD1 is a putative suppressor of squamous cell carcinomas of the head and neck, 24 and the gene encodes a 389-kDa transmembrane protein named for its repeated CUB and sushi domains. 24 Both CUB and sushi domains are found in many other proteins and are believed to be sites of either proteinprotein or protein-ligand interactions. 25,26 At this moment, it is not clear how CSMD1 would contribute to blood pressure regulation.…”

Section: à4mentioning

confidence: 99%