Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck

Pearlstein, Richard P.; Benninger, Michael S.; Carey, Thomas E.; Zarbo, Richard J.; Torres, Frank X.; Rybicki, Benjamin A.; Dyke, Daniel L. Van

doi:10.1002/(sici)1098-2264(199804)21:4<333::aid-gcc7>3.0.co;2-#

Cited by 70 publications

(50 citation statements)

References 29 publications

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“…5 Consistently with our findings, allelic loss on chromosome 8p have been associated with advanced tumor stages and poor survival 20 -22 similar to 11qter and 18q deletions. 10,23,24 However, our study also revealed further loci on several other chromosome arms.…”

Section: Discussionsupporting

confidence: 48%

Genetic Imbalances with Impact on Survival in Head and Neck Cancer Patients

Bockmühl

Schlüns

Küchler

et al. 2000

The American Journal of Pathology

113

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Chromosomal imbalances in 113 primary head and neck squamous cell carcinomas (HNSCCs) determined by comparative genomic hybridization were correlated with patients survival using custom-made computer software which enabled the assessment of individual chromosomal loci. The Kaplan-Meier analysis revealed that overrepresentations of 2q12, 3q21-29, 6p21.1, 11q13, 14q23, 14q24, 14q31, 14q32, 15q24, 16q22, and deletions of 8p21-22 and 18q11.2 were significantly associated with both shorter disease-free interval and disease-specific survival in this tumor collective. Multivariate Cox proportional hazards regression models consistently identified the gains of 3q21-29, 11q13, and the loss of 8p21-22 as independent prognostic markers carrying a higher significance than the nodal status as the only clinicopathological parameter with statistical importance. In addition, these three markers allowed a molecular dissection of the patients with low clinical risk (pN0 and pT2 tumors). Thus, the genomic data being derived from the evaluation of primary HNSCC enabled a stratification of the patients into subgroups with different survival highlighting the necessity of a genetically based tumor classification for refining diagnosis and treatment of HNSCC patients. (Am J Pathol , :369 -375)

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Section: Discussionsupporting

confidence: 48%

Genetic Imbalances with Impact on Survival in Head and Neck Cancer Patients

Bockmühl

Schlüns

Küchler

et al. 2000

The American Journal of Pathology

113

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“…7,38 -41 Lastly, this study failed to confirm our earlier findings that loss of heterozygosity at 18q was associated with poor survival. 42 Although recruitment for the previous work as well as the current inquiry both occurred at Henry Ford Hospital in Detroit, Michigan, there was no overlap in the 2 study populations. Differences in recruitment methods exist between the 2 studies.…”

Section: Discussionmentioning

confidence: 97%

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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“…TSG implicated in HNSCC carcinogenesis and located on chromosomes 8p and 18q remain to be identified. The presence of LOH on 18q is of particular interest since it was related to tumor stage and prognosis (Pearlstein et al, 1998). This correlation was also found in other types of tumors (i.e.…”

Section: Introductionmentioning

confidence: 86%

Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma

et al. 2002

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The 18q chromosome arm is frequently lost in advanced head and neck squamous cell carcinoma. Twenty-four microsatellite markers located on chromosome 18q were genotyped in 145 primary tumors and 10 cell lines in order to identify putative tumor suppressor genes implicated in tumor progression. Two different minimal common regions of loss (MCRL) were identified at 18q22 and 18q23 respectively. To refine and delineate boundaries of an homozygous deletion found in one cell line, 44 extra markers located at 18q22 were analysed and the homozygous deletion was precisely defined within a critical region of 4.9 Mb. Four known genes (CDH7, CDH19, DNAM-1, FLJ23594) located in this critical region and two EST clusters (Hs.96900, Hs.98628) were selected for further investigations. For these six genes, genomic structures were established, somatic mutations were screened in 20 HNSCC and 10 cell lines and transcription levels were determined in eight cell lines. No somatic mutations were found in any of the candidate genes analysed (57 coding exons). However, differential transcription levels were observed for CDH19 and Hs.96900 in head and neck cancer cell lines supporting their putative involvement through down regulation mechanisms in head and neck cancer progression.

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Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck

Cited by 70 publications

References 29 publications

Genetic Imbalances with Impact on Survival in Head and Neck Cancer Patients

Genetic Imbalances with Impact on Survival in Head and Neck Cancer Patients

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

Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma

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