Molecular Genetics of Head and Neck Cancer

Gleich, Lyon L.; Salamone, Frank N.

doi:10.1177/107327480200900502

Cited by 74 publications

(75 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[24][25][26][27][28] However, some previous reports did not find any prognostic significance of p53 in head and neck cancers. 29 Recently, Balz et al 30 reported that 95% of the head and neck cancers lack normal p53 function and concluded that inactivation of p53 per se is not a suitable choice as a prognostic or predictive marker. Since prognosis has a multifactorial molecular background, it is important to look for a battery of markers for its influence on the prognosis of the patients in a larger cohort.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma

Jayasurya¹,

Sathyan²,

Lakshminarayanan³

et al. 2005

Modern Pathology

View full text Add to dashboard Cite

The two well-defined pathways that are shown to be prominently altered in a variety of cancers are the cell cycle regulatory pathways led by either p53 or Rb genes. The present study is undertaken to find the pathway that is more altered in oral carcinoma at protein level, with special emphasis on its prognostic significance. The expression pattern of key molecules of the Rb and p53 pathways, such as Rb, cyclin D1, CDK4, p16, p53, p21 and Bcl-2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique. The expression index of these molecules and various clinicopathological factors were statistically correlated with treatment end points to assess its prognostic efficacy after following up these patients up to a maximum of 48 months with a median of 23 months. Rb pathway proteins, Rb (P ¼ 0.016), cyclin D1 (P ¼ 0.0001) and p16 (P ¼ 0.012) showed significant association with disease-free survival, and p16 (P ¼ 0.041) and cyclin D1 (P ¼ o0.0001) with the overall survival. Among p53 pathway proteins studied, only p53 expression index showed association with both disease-free survival and overall survival. Multivariate analyses confirmed that the biological variables, cyclin D1 and p16 and the clinical variable, 'stage of disease' were independent predictors of disease-free survival and overall survival. Subgrouping of the patients on the basis of p16 and cyclin D1 expression revealed that the subgroup having downregulation of p16 and overexpression of cyclin D1 exhibited the worst disease-free survival and overall survival compared to the other subgroups. The present data showed that disabling of the Rb and p53 pathways were frequent events in oral carcinoma. The study also demonstrated that the Rb pathway proteins are comparatively more important than p53 pathway proteins for the prognostication of oral carcinoma patients. The combined evaluation of p16 and cyclin D1 in oral carcinoma could identify a group of patients with the worst survival who might therefore need alternate or more intense treatment strategies. Oral cancer is one of the 10 most common cancers in the world and is commonest in India and other south-east Asian countries.1 In India, oral cancer is highly prevalent, comprising a large fraction of all malignancies, due to the habit of tobacco chewing alone or with betel quid, which is commonly observed in the population.2 Although recent advances have reduced the morbidity of oral cancer, the 5-year survival rate for these patients has remained almost unchanged at B50% for the last 30 years.3 Oral cancers are highly heterogeneous in nature regarding site, biology and treatment response. In clinical practice, the treatment planning and prognosis of oral cancer is mainly based on the TNM classification; however, there is increasing evidence that in its current form, it is probably insufficient to predict the clinical outcome of patients with oral carcinoma. Therefore, it is important to look for new biological prognostic markers that might add inform...

show abstract

Section: Discussionmentioning

confidence: 99%

Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma

Jayasurya¹,

Sathyan²,

Lakshminarayanan³

et al. 2005

Modern Pathology

View full text Add to dashboard Cite

show abstract

“…CCND1'in aktivitesi G1 fazı süresince maksimum seviyede kalır ve p16, p21 ve p27 gibi tümör baskılayıcı genler tarafın-dan inhibe edilebilir. 5 Meme, baş-boyun, özofagus, larinks ve akciğer gibi çeşitli kanserlerde CCND1 aktivasyonu ya da aşırı ekspresyonunun gözlen-mesi CCND1'deki değişikliklerin karsinogenezde rol oynadığını düşündürmektedir. 6,7 Yapılan çalış-malarda HNC'de, tümörlerin %18-%58'inde CCND1 amplifikasyonu gözlenmiş, 8,9 genin amplifikasyonu ya da aşırı ekspresyonu, nüks, nodal metastaz ve ölümle ilişkilendirilmiştir.…”

Section: Baş-boyun Kanserli Hastalarda Siklin D1unclassified

Analysis of Cyclin D1 G87 A Polymorphism in Patients with Head and Neck Cancers

Demokan¹,

Süoğlu²,

Ulusan³

et al. 2011

Turkiye Klinikleri J Med Sci

View full text Add to dashboard Cite

Ö ÖZ ZE ET T A Am ma aç ç: : Baş-bo yun kan ser le ri (HNC) dün ya da en yay gın kan ser ler ara sın da al tın cı sı ra da yer al makta dır. Ya pı lan ça lış ma lar ge ne tik yat kın lı ğın bu kan se re ya ka lan ma ris ki açı sın dan önem li bir rol oy nadı ğı nı gös ter mek te, hüc re sik lu su nun dü zen len me sin de gö rev alan Sik lin D1 (CCND1) ge nin de ki bir po li mor fiz min ge ne tik yat kın lı ğın al tın da ya tan ne den ol du ğu dü şü nül mek te dir. Li te ra tür de HNC'de CCND1 gen po li mor fiz miy le ya pıl mış az sa yı da ça lış ma bu lun mak ta dır. Türk HNC has ta la rın da bu poli mor fiz mi in ce le yen ça lış ma ise mev cut de ğil dir. Ça lış ma mız da, CCND1 ge nin de ki G870A po li mor fizmi in ce len miş ve al lel ve ge no tip da ğı lım la rı ile kli nik pa ra met re ler ara sın da ki iliş ki de ğer len di ril miş tir. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Ça lış ma kap sa mın da, baş-bo yun kan ser li 95 has ta nın pe ri fe rik kan ör nek le ri ile sağ lık lı 40 ki şi ye ait pe ri fe rik kan ör nek le ri in ce len miş tir. Top la nan ör nek ler den DNA el de edil dik ten son ra CCND1 ge ni ne öz gü po li mor fik böl ge polimeraz zincir reaksiyonu ile ço ğal tıl mış, son ra uy gun res trik si yon en zi mi kul la nı la rak ke sil miş ve so nuç lar vi de o-gel dö kü man tas yon sis te mi yar dı mıy la değer len di ril miş tir. Po li mor fik da ğı lım lar, Fi net ti va ka-kon trol is ta tis tik prog ra mı kul la nı la rak sağ lık lı kişi ler de ki al lel fre kans la rı ile kı yas lan mış ve χ 2 (Ki-ka re) test le ri ile has ta la rın kli nik ve pa to lo jik bul gu la rıy la iliş ki le ri araş tı rıl mış tır. B Bu ul l g gu u l la ar r: : Baş-bo yun kan ser li has ta lar la kon trol gru bu ara sın da allel ve ge no tip da ğı lım la rı açı sın dan an lam lı bir fark göz len mez ken, yas sı epi tel hüc re li (YEH)-dı şı hasta lar da GA he te ro zi got ge no ti pi ile kom bi ne GA + AA ge no tip le ri dü şük has ta lık ris kiy le iliş ki li bu lun muş tur. Ay rı ca YEH kan ser gru bun da YEH-dı şı has ta la ra oran la A al le li ne an lam lı de re ce de sık rast lan mış tır. S So o n nu uç ç: : Baş-bo yun kar si no ge ne zin de tü mö rün his to lo ji si ne gö re CCND1 ge ni nin de ği şik var yant la rı nın et ki li ola bi le ce ği dü şü nül mek te dir.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Çok biçimlilik, tek nükleotid; siklin D1, baş ve boyun tümörleri A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : He ad and neck can cer (HNC) is the sixth le a ding can cer among the most frequent can cers worl dwi de. Stu di es in di ca te that ge ne tic pre dis po si ti on plays an im por tant ro le for HNC risk and a poly morp hism in cyclin D1 (CCND1) ge ne ta king part in re gu la ti on of cell cycle is con si dered to be the un derl ying ca u se of ge ne tic pre dis po si ti on. A few stu di es are ava i lab le in li te ra tu re on CCND1 ge ne poly morp hism in HNC. No stu di es are ava i lab le in li te ra tu re investigating this poly morphism in Tur k...

show abstract

“…Approximately 80-90% of cases of HNSCC are attributed to prolonged tobacco and/or alcohol use (2). However, only a small fraction of those who consume tobacco or alcohol develop this disease, suggesting that genetic factors are also important in its pathogenesis (4)(5)(6). Fundamental to the genetic basis of all cancers is the overexpression of oncogenes and/or silencing of tumor suppressor genes.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Rab25 activates Akt1 in head and neck squamous cell carcinoma

et al. 2015

View full text Add to dashboard Cite

Abstract. Several studies have suggested that Ras-associated binding 25 protein (Rab25) is involved in the pathogenesis of human cancer. Although it has been demonstrated that the development of head and neck squamous cell carcinoma (HNSCC) is the result of an accumulation of multiple sequential genetic and epigenetic alterations in key genes with important functions in cell growth and the cell cycle, recent studies have indicated that HNSCC is a complex and heterogenous disease. To the best of our knowledge, there is no data regarding the regulation of the Rab25 gene at the mRNA or protein level in HNSCC. Furthermore, available data on Rab25 expression in other types of cancer are conflicting. The aim of the present study was to investigate whether Rab25 is involved in the development and/or progression of HNSCC, and to analyze the mechanisms underlying its effects in this type of cancer. The expression of Rab25 mRNA in HNSCC tissues and adjacent non-tumor tissue samples was measured using reverse transcription-quantitative polymerase chain reaction, while the level of the Rab25, Akt1 and phosphorylated-Akt1 proteins was measured using western blotting. Expression of Rab25 mRNA and protein was downregulated in 69.1% and 56.1% of tumor tissue samples, respectively. This downregulation was associated with an increase in p-Akt1 expression, in the absence of a change in total Akt1 protein levels, in tumor tissues compared with normal tissues. The current findings suggest that Rab25 acts as a tumor suppressor in HNSCC.

show abstract

Molecular Genetics of Head and Neck Cancer

Abstract: Head and neck cancers comprise a complex genetic disease. Although much has been learned about the molecular genetics of head and neck cancers, continued study of multiple genes is critical for further progress. Gene therapy, although promising, must also overcome this complexity.

Cited by 74 publications

References 85 publications

Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma

Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma

Analysis of Cyclin D1 G87 A Polymorphism in Patients with Head and Neck Cancers

Downregulation of Rab25 activates Akt1 in head and neck squamous cell carcinoma

Contact Info

Product

Resources

About