scholarly journals APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1666 ◽  
Author(s):  
Daniel L. Faden ◽  
Krystle A. Lang Kuhs ◽  
Maoxuan Lin ◽  
Adam Langenbucher ◽  
Maisa Pinheiro ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Common Mechanism ◽  
Induced Mutations ◽  
Viral Genomes ◽  
Definitive Evidence ◽  
The Mean ◽  
First Time ◽  
Variant Allele Fraction

APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0–29) mutations per genome. The mean of APOBEC mutations in viral genomes was one (range 0–5). Viral APOBEC mutations, compared to non-APOBEC mutations, were more likely to be low-variant allele fraction mutations, suggesting that APOBEC mutagenesis actively occurrs in viral genomes during infection. HPV16 APOBEC-induced mutation patterns in OPSCC were similar to those previously observed in cervical samples. Paired host and viral analyses revealed that APOBEC-enriched tumor samples had higher viral APOBEC mutation rates (p = 0.028), and APOBEC-associated RNA editing (p = 0.008), supporting the concept that APOBEC mutagenesis in host and viral genomes is directly linked and occurrs during infection. Using paired sequencing of host somatic exomes, transcriptomes, and viral genomes, we demonstrated for the first-time definitive evidence of concordance between tumor and viral APOBEC mutagenesis. This finding provides a missing link connecting APOBEC mutagenesis in host and virus and supports a common mechanism driving APOBEC dysregulation.

scholarly journals APOBEC Mutagenesis is Concordant Between Tumor and Viral Genomes in HPV Positive Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Daniel L Faden ◽  
Krystle A. Lang Kuhs ◽  
Maoxuan Lin ◽  
Adam Langenbucher ◽  
Maisa Pinheiro ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Common Mechanism ◽  
Induced Mutations ◽  
Mrna Editing ◽  
Viral Genomes ◽  
Viral Restriction ◽  
Hotspot Mutations ◽  
Editing Enzyme

AbstractAPOBEC (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like) is a major mutagenic source in human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Why APOBEC mutations predominate in HPV+OPSCC remains an area of active investigation. Prevailing theories focus on APOBECs role as a viral restriction agent. APOBEC-induced mutations have been identified in both human cancers and HPV genomes, but whether they are directly linked in HPV+OPSCCs remains unknown. We performed sequencing of host somatic exomes, transcriptomes and HPV16 genomes from 79 HPV+ OPSCC samples, quantifying APOBEC mutational burden and activity in both the host and virus. APOBEC was the dominant mutational signature in somatic exomes. APOBEC vulnerable PIK3CA hotspot mutations were exclusively present in APOBEC enriched samples. In viral genomes, there was a mean (range) of 5 (0-29) mutations per genome. Mean (range) of APOBEC mutations in the viral genomes was 1 (0-5). Viral APOBEC mutations, compared to non-APOBEC mutations, were more likely to be low-variant allele frequency mutations, suggesting that APOBEC mutagenesis is actively occurring in viral genomes during infection. Paired host and viral analyses revealed that APOBEC-enriched tumor samples had higher viral APOBEC mutation rates (p=0.028), and APOBEC-associated RNA editing (p=0.008) suggesting that APOBEC mutagenesis in host and viral genomes are directly linked. Using paired sequencing of host somatic exomes, transcriptomes, and viral genomes from HPV+OPSCC samples, here, we show concordance between tumor and viral APOBEC mutagenesis, suggesting that APOBEC-mediated viral restriction results in off-target host-genome mutations. These data provide a missing link connecting APOBEC mutagenesis in host and virus and support a common mechanism driving APOBEC dysregulation.

scholarly journals Comparison of Androgen Receptor, VEGF, HIF-1, Ki67 and MMP9 Expression between Non-Metastatic and Metastatic Stages in Stromal and Tumor Cells of Oral Squamous Cell Carcinoma

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 336
Author(s):  
Lovorka Batelja-Vuletic ◽  
Cedna Tomasovic-Loncaric ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
Aleksandra Fucic ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Squamous Cell ◽  
Mmp9 Expression ◽  
Oral Malignancy ◽  
First Time ◽  
Epithelium Cells ◽  
Diagnostics And Therapy

Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral malignancy with low survival as it is very often diagnosed at an advanced stage, which is why the accurate profiling of the tumor is essential. The aim of this study was to, for the first time, compare in OSCC the frequency of AR, VEGF, MMP9, HiF1beta and Ki67 between the non-metastatic and metastatic disease. Materials and Methods: In the study, 96 non-metastatic and 91 metastatic OSCC patients were analysed for AR, VEGF, MMP9, HiF1beta and Ki67 levels by immunohistochemistry. Results: All of the tested biomarkers significantly differed between non-metastatic and metastatic disease. A significant association was found between >/=20% AR positive epithelium cells in cytoplasm, Ki67 and VEGF in cancer stroma. Ki67, HiF1beta, VEGF and MMP9 were significantly associated with TNM stages. Conclusion: Our results show for the first time an interplay between AR, VEGF, MMP9, HiF1beta and Ki67 in OSCC which may contribute to better diagnostics and therapy selection.

scholarly journals Case of development of Gottron’s carcinoid papillomatosis of skin against a background of protracted psoriasis

2020 ◽  
Vol 36 (6) ◽  
pp. 76-82
Author(s):  
M. Yu. Kobernik ◽  
V. D. Elkin ◽  
T. G. Sedova ◽  
A. A. Zhukova
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clinical Picture ◽  
Skin Disease ◽  
Clinical Observation ◽  
Lower Extremities ◽  
Pseudoepitheliomatous Hyperplasia ◽  
First Time

The paper presents information regarding a rare skin disease Gottrons carcinoid papillomatosis, for the first time described in 1932 by German dermatologist H.A. Gottron. Its development is associated with the preceding chronic dermatoses and disturbance of circulation in the lower extremities. Morphologically, Gottrons carcinoid papillomatosis of the skin is characterized by the development of pseudoepitheliomatous hyperplasia of epidermis. Clinical picture, dermatoscopy, ultrasound and histological studied were used for diagnosis. This disease should be differed from high differentiated squamous cell carcinoma of the skin, chronic ulcerous pyodermavegetans, lupus verrucosis, chromomycosis. We described our own clinical observation of Gottrons carcinoid papillomatosis of the skin, developed against a background of psoriasis.

Epidemiological profile of esophageal cancer at the Joliot Curie Institute in Dakar in 2018

2021 ◽  
Vol 1 (1) ◽  
pp. 24-25
Author(s):  
Mohammed Ezzet Charfi ◽  
Abdoul Halim Bagué ◽  
Awaleh Ahmed Awaleh ◽  
Sidy Ka ◽  
Ahmadou Dem
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Adenosquamous Carcinoma ◽  
Young Patients ◽  
The World ◽  
The Mean ◽  
Epidemiological Profile ◽  
Consultation Time

INTRODUCTION: Esophageal cancer is one of the most common cancers in the world affecting males more often than females and with a poor prognosis. The aim of our work was to describe the epidemiology of patients followed for esophageal cancer at the Joliot-Curie Institute in 2018. MATERIALS AND METHODS: This is a descriptive retrospective study including all patients followed at the institute from January 1, 2018 to December 31, 2018 for esophageal cancer with histological evidence. RESULTS: We collected 93 patients referred to the institute for the management of esophageal cancer, 46 women (49.5%) and 47 men (50.5%). The mean age was 49 years with a median age of 50 and extremes of 22 and 84 years. The notion of smoking was found in 24 patients (25.8%) exclusively men (51%), associated in six cases with a notion of alcoholism. The median consultation time was five months. The main circumstance of discovery remains dysphagia (87.1%), followed by aphagia (4.3%) and odynophagia (4.3%). Squamous cell carcinoma is the most represented histological type with 89 patients (95.7%) distributed as follows: 45 women and 44 men. Adenocarcinoma was found in three cases (two men and one woman) and finally one case of adenosquamous carcinoma. CONCLUSION: Squamous cell carcinoma is the most frequent esophagus cancer. It represents the fifth location in our institute and occurs in young patients without gender predominance.

scholarly journals Narrow band imaging under less-air condition improves the visibility of superficial esophageal squamous cell carcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Taro Iwatsubo ◽  
Ryu Ishihara ◽  
Yasushi Yamasaki ◽  
Yusuke Tonai ◽  
Kenta Hamada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Color Change ◽  
Narrow Band ◽  
Narrow Band Imaging ◽  
Endoscopic Observation ◽  
Flat Type ◽  
The Mean ◽  
Visibility Score

Abstract Background The current virtual chromoendoscopy equipment cannot completely detect superficial squamous cell carcinoma (SCC) in the esophagus, despite its development in the recent years. Thus, in this study, we aimed to elucidate the appropriate air volume during endoscopic observation to improve the visibility of esophageal SCC. Methods This retrospective study included a total of 101 flat type esophageal SCCs identified between April 2017 and January 2019 at the Department of Gastrointestinal Oncology, Osaka International Cancer Institute. Video images of narrow band imaging (NBI) under both less-air and standard-air conditions were recorded digitally. Videos were evaluated by five endoscopists. Relative visibility between less-air and standard-air conditions of the brownish area, brownish color change of the epithelium, and dilated intrapapillary capillary loop (IPCL) were graded as 5 (definitely better under less-air condition) to 1 (definitely worse under less-air condition), with 3 indicating average visibility (equivalent to standard-air observation). Results The mean (standard deviation) visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs under less-air condition were 3.94 (0.58), 3.73 (0.57), and 4.13 (0.60), respectively, which were significantly better than that under standard-air condition (p < 0.0001). Esophageal SCC evaluated as ≥ 4 in the mean visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs accounted for 50% (51/101 lesions), 34% (34/101 lesions), and 67% (68/101 lesions), respectively. Conclusions The present results suggested that NBI with less air might improve the visibility of flat type esophageal SCC compared with NBI with standard air. Less-air NBI observation may facilitate the detection of flat type esophageal SCC. Trial registration The present study is a non-intervention trial.

Erosive pustulöse Dermatose der Kopfhaut: häufig übersehen und selten diagnostiziert

2020 ◽  
Vol 8 (1) ◽  
pp. 21-22
Author(s):  
Markus Braun-Falco
Keyword(s):  
Squamous Cell Carcinoma ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Actinic Keratosis ◽  
Diagnostic Delay ◽  
Case Series ◽  
Older Men ◽  
Uncommon Disease ◽  
First Time

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon disease and primarily affects older men who have photodamaged bald scalp, as was confirmed by our case series. EPDS is probably an overlooked disease, whose diagnosis is often missed because of a higher incidence of other cutaneous diseases affecting the same area and usually secondary to chronic actinic damage, such as actinic keratosis, basal cell carcinoma, and squamous cell carcinoma. For the first time, we report a case series of misdiagnosed EPDS with the aim of understanding why a diagnosis of EPDS was initially missed and try to give some tips to avoid future diagnostic delay.

Malignant Transformation of Mature Cystic Teratoma: Is Squamous Cell Carcinoma Different From the Other Types of Neoplasm?

2018 ◽  
Vol 28 (9) ◽  
pp. 1650-1656 ◽  
Author(s):  
Munetoshi Akazawa ◽  
Sachiko Onjo
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Malignant Transformation ◽  
Squamous Cell ◽  
Clinical Characteristics ◽  
Case Series ◽  
Cystic Teratoma ◽  
The Other ◽  
The Mean

ObjectivesMalignant transformation of mature cystic teratoma (MCT) is rare. Unlike squamous cell carcinoma (SCC) in MCT, the other types of neoplasm in MCT have not been discussed in publications. We analyzed the clinical characteristics and prognosis of the other types of neoplasm (non-SCC) compared with those of SCC.MethodsA systematic literature search of literature published from 2000 to 2017 was conducted in PubMed, Web of Science, and Scopus. We reviewed case series that included all pathological types of malignant transformation.ResultsA total of 155 cases from 15 case series, including our cases, were included. Of the cases, 90 (58%) were SCC and 65 (42%) were non-SCC, including adenocarcinoma, carcinoid tumor, thyroid carcinoma, sarcoma, adenosquamous carcinoma, melanoma, sebaceous carcinoma, oligodendroglioma, signet ring cell carcinoma, and transitional cell carcinoma, in descending order of frequency. The mean ages of patients with SCC and non-SCC were 50.5 and 48.9 years, respectively. The mean tumor sizes were 14.7 cm in SCC and 13.9 cm in non-SCC. Surgical approaches were similar. First-line chemotherapy for epithelial ovarian cancers was the most commonly used regimen in SCC and non-SCC. Overall survival did not differ significantly, showing better prognosis in stage I and poor prognosis in stages II, III, and IV. A difference in overall survival was observed among pathological types of non-SCC.ConclusionsClinical characteristics and outcomes did not differ significantly between SCC and non-SCC. However, chemotherapy regimens differed to some extent, and the possibility of difference in overall survival among pathological types of non-SCC was suggested.

Changing Incidence of Invasive Adenocarcinoma of the Uterine Cervix in East Anglia

1997 ◽  
Vol 4 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Diane Stockton ◽  
Pauline Cooper ◽  
R N Lonsdale
Keyword(s):  
Cervical Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Birth Cohort ◽  
Squamous Cell ◽  
Uterine Cervix ◽  
Invasive Adenocarcinoma ◽  
East Anglia ◽  
The Mean ◽  
Age Shift

Objective— To determine trends in incidence of invasive adenocarcinoma of the uterine cervix in East Anglia. Methods— Cervical cancer incidence data for both squamous cell carcinomas and adenocarcinomas were obtained from the East Anglian Cancer Registry for the period 1971–94. Similar data were obtained for England and Wales. European age standardised rates (ASRs) were used for comparisons. Results— The mean incidence (ASR) of cervical adenocarcinoma was 0.85 per 10s in 1971–76, rising to 2.54 per 105 in 1989–94. There has been a marked age shift, with the main increase in incidence occurring in younger women aged 30–39. The mean incidence (ASR) of squamous cell carcinoma of the cervix has decreased from 9.78 to 8.74 per 10s over the periods 1971–76 and 1989–94. Again there has been an age shift, moving from a single incidence peak in the 4S-S9 age band in earlier years to incidence peaks in both the 30–39 and 55–69 age bands in more recent years. Similar trends were noted when data for England and Wales were analysed. Birth cohort analyses show that both tumours are occurring progressively earlier (about five years earlier in each five year birth cohort). Conclusion— Although the overall incidence of cervical carcinoma is declining, this study has shown an increased incidence of cervical adenocarcinoma, particularly in the younger age groups. In future it would seem advisable to publish separate incidence and mortality data for squamous cell carcinoma and adenocarcinoma of the uterine cervix. All practitioners involved in the cervical cancer screening programme would then be aware of the very real significance of this tumour.

Association of polymorphisms in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription factors (IKBKAP and ZNF415) with base of tongue squamous cell carcinoma risk.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6073-6073
Author(s):  
Carmen Silvia Passos Lima ◽  
Benilton Carvalho ◽  
Renata Pellegrino ◽  
Leticia Khater ◽  
Carlos Takahiro Chone ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dna Microarrays ◽  
Tongue Squamous Cell Carcinoma ◽  
Nucleotide Polymorphisms ◽  
Dna Transcription ◽  
Base Of Tongue ◽  
First Time

6073 Background: Recently, we found 6.609 genetic single nucleotide polymorphisms (SNPs) with distinct frequencies between base of tongue squamous cell carcinoma (BTSCC) patients and controls. The study was performed using high-resolution DNA microarrays genotyping (Affymetrix). The SNPs identified never have been previously described with BTSCC risk. Some SNPs of interest were located in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription (IKBKAP and ZNF415) and they were selected to validation process. Objective: Validate the SNPs ERP29 c.*293A>G (rs7114); LEF1 c.*1213A>G (rs2107028) and g.127267A>G (rs4245926); MCC c.*5077A>G (rs7033); PTCH1 g.27369025G>A (rs16909856) and g.27369324G>A (rs16909859); IKBKAP c.3214T>A (rs3204145) and ZNF415 c.*443A>G (rs3814) associated to BTSCC risk. Methods: Genomic DNA from 49 BTSCC patients and 49 controls was genotyping by TaqMan assays (Applied Biosystems). The differences between groups were analyzed by logistic regression model. Power analysis (PA) was used to verify the effect of sample size on the results obtained. Results: Eight SNPs identified by Affymetrix were validated by TaqMan assays. The frequencies of ERP29 c.*293AG+GG (30 vs 11%, P=0.03; PA=65%), LEF1 c.*1213AA+AG (95 vs 80%, P=0.02; PA=61%) and g.127267AA+AG (93 vs 78%, P=0.02; PA=56%), MCC c.*5077AA+AG (85 vs 64%, P=0.008; PA=67%), PTCH1 g.27369025GG+GA (90 vs 73%, P=0.005; PA=58%) and g.27369324GG+GA (90 vs 73%, P=0.008; PA=58%), IKBKAP c.3214TT+TA (90 vs 72%, P=0.01; PA=62%) and ZNF415 c.*443AA+AG (59 vs 41%, P=0.02; PA=43%) were more common in patients than in controls. Individuals with these genotypes were at 2.9(CI95%: 1.1-8.4), 3.9 (CI95%: 1.4-11.2), 4.0 (CI95%: 1.2-14.7), 3.5 (CI95%: 1.2-11.9), 5.0 (CI95%: 1.7-16.9), 4.5 (CI95%: 1.5-15.2), 4.1 (CI95%: 1.4-12.9), and 3.9 (CI95%: 1.2-13.7)-fold increased risks for BTSCC than others, respectively. Conclusions: Our data present for the first time evidence that inherited abnormalities in ERP29, MCC, LEF1, PTCH1, IKBKAP, and ZNF415 genes may be important determinants of BTSCC. Financial support: FAPESP and FINEP.

Salvage endoscopic submucosal dissection for the treatment of esophageal squamous cell carcinoma after local treatment failure with chemotherapy, radiotherapy, or chemoradiotherapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 148-148
Author(s):  
Toshiro Iizuka ◽  
Daisuke Kikuchi ◽  
Shu Hoteya ◽  
Akihiro Yamada ◽  
Mitsuru Kaise
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Esophageal Squamous Cell Carcinoma ◽  
Treatment Failure ◽  
Endoscopic Submucosal Dissection ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Local Treatment ◽  
Submucosal Dissection ◽  
The Mean

148 Background: Chemotherapy (CT), radiotherapy (RT), and chemoradiotherapy (CRT) are efficacious treatment options for esophageal squamous cell carcinoma (ESCC). However, local treatment failure remains a major problem. In this study, we applied endoscopic submucosal dissection (ESD) for the treatment of ESCC after local treatment failure with CT, RT, or CRT. The efficacy, safety, and feasibility of salvage ESD were assessed. Methods: Between 2008 and 2014, 611 patients underwent ESD for superficial ESCC in our hospital. Of them, 14 required salvage ESD: 7 for local treatment failure after CT, 4 after CRT, and 3 after RT. Each patient was treated with CT using 5-fluorouracil + cisplatin or RT, which consisted of >50 Gy of irradiation with or without concurrent CT. The following clinical findings were confirmed in all patients: no evidence of lymph node or distant metastasis after treatment, and an endoscopically resectable lesion. Results: The male to female ratio was 11:3 and the mean age was 64.9 (44-81) years. Clinical stages before treatment were T1b/T2/T3/T4 in 10/1/2/1, N0/1 in 7/7, and M0/1 in 13/1, respectively. The mean tumor size was 18.6 mm, and the mean procedure time was 45.7 min. En bloc resection was achieved in 100% of cases, and the R0 resection rate was 78.6%. Histopathological assessment of specimens taken at salvage ESD revealed that 6 lesions (42.9%) had invaded the submucosal layer and had been resected noncuratively because of a positive vertical margin (n = 2) or positive lymphovascular invasion (n = 5). No immediate or delayed complications, including major bleeding or perforation, and no ESD-related deaths occurred. At a mean follow-up period of 26.5 (range, 5–55) months, local recurrence had developed at the treatment site in 2 patient. Overall, 10 patients were still alive. The remaining 4 had developed lymph node metastasis, 2 of whom had died from it. Conclusions: Salvage ESD is an option for ESCC patients with local treatment failure after CT, RT, or CRT.

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