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Article ; Online: Machine learning to detect the SINEs of cancer.

Douville, Christopher / Lahouel, Kamel / Kuo, Albert / Grant, Haley / Avigdor, Bracha Erlanger / Curtis, Samuel D / Summers, Mahmoud / Cohen, Joshua D / Wang, Yuxuan / Mattox, Austin / Dudley, Jonathan / Dobbyn, Lisa / Popoli, Maria / Ptak, Janine / Nehme, Nadine / Silliman, Natalie / Blair, Cherie / Romans, Katharine / Thoburn, Christopher /

Gizzi, Jennifer / Schoen, Robert E / Tie, Jeanne / Gibbs, Peter / Ho-Pham, Lan T / Tran, Bich N H / Tran, Thach S / Nguyen, Tuan V / Goggins, Michael / Wolfgang, Christopher L / Wang, Tian-Li / Shih, Ie-Ming / Lennon, Anne Marie / Hruban, Ralph H / Bettegowda, Chetan / Kinzler, Kenneth W / Papadopoulos, Nickolas / Vogelstein, Bert / Tomasetti, Cristian

Science translational medicine

2024 Volume 16, Issue 731, Page(s) eadi3883

Abstract: We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing ...

Abstract	We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature-the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer.
MeSH term(s)	Humans ; Reproducibility of Results ; Neoplasms/diagnosis ; Neoplasms/genetics ; Short Interspersed Nucleotide Elements ; Machine Learning ; Aneuploidy
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.adi3883
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Zs.A 6941: Show issues

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Article ; Online: Clinical Characteristics of Multiple Colorectal Adenoma Patients Without Germline APC or MYH Mutations.

Tieu, Alan H / Edelstein, Daniel / Axilbund, Jennifer / Romans, Katharine E / Brosens, Lodewijk A / Wiley, Elizabeth / Hylind, Linda / Giardiello, Francis M

Journal of clinical gastroenterology

2015 Volume 50, Issue 7, Page(s) 584–588

Abstract: Background: Patients with multiple colorectal adenomas (MCRA) without genetic cause are increasingly being diagnosed. The characteristics and natural history of this condition are not well studied.: Materials and methods: Twenty-seven patients with ... ...

Abstract	Background: Patients with multiple colorectal adenomas (MCRA) without genetic cause are increasingly being diagnosed. The characteristics and natural history of this condition are not well studied. Materials and methods: Twenty-seven patients with MCRA, with cumulatively 10 to 99 colorectal adenomas and without deleterious mutations of APC or MYH genes, were investigated. Results of colonoscopies with a mean follow-up of 4.9 years (range, 0 to 27 y) were evaluated. Findings from esophagogastroduodenoscopy and extracolonic manifestations were assessed. Results: The mean age at polyp diagnosis and MCRA diagnosis was 47.8±13.1 years (range, 21 to 72 y) and 50.4±14.6 years (range, 21 to 72 y), respectively. In 22% of patients another family member had MCRA. At first colonoscopy, the mean number of adenomas was 35.0±35.9 (range, 0 to 99). Serrated polyps were rare. Esophagogastroduodenoscopy revealed 47% of patients had upper tract neoplasia. Patients with upper tract findings were diagnosed with MCRA at significantly younger mean age than those without findings, P<0.05. Eighteen patients (67%) underwent colectomy with a mean time from diagnosis of MCRA of 3.1±1.3 years. After surgery, surveyed patients developed recurrent adenomas in retained colorectum. Nine patients (33%) had extracolonic cancers. Conclusions: MCRA patients have a similar clinicopathologic phenotype to known syndromes of attenuated adenomatous polyposis and the majority have need for colectomy. The management of MCRA patients and families should parallel that of attenuated familial adenomatous polyposis and MUTYH-associated polyposis including surveillance of the upper tract.
MeSH term(s)	Adenoma/diagnosis ; Adenoma/pathology ; Adenoma/surgery ; Adenomatous Polyposis Coli Protein/genetics ; Adult ; Aged ; Colectomy/methods ; Colonoscopy/methods ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/surgery ; DNA Glycosylases/genetics ; Endoscopy, Digestive System ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Phenotype ; Retrospective Studies ; Young Adult
Chemical Substances	APC protein, human ; Adenomatous Polyposis Coli Protein ; DNA Glycosylases (EC 3.2.2.-) ; mutY adenine glycosylase (EC 3.2.2.-)
Language	English
Publishing date	2015-10-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	448460-5
ISSN	1539-2031 ; 0192-0790
ISSN (online)	1539-2031
ISSN	0192-0790
DOI	10.1097/MCG.0000000000000416
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Zs.A 1523: Show issues

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Article ; Online: Serrated polyposis: rapid and relentless development of colorectal neoplasia.

Edelstein, Daniel L / Axilbund, Jennifer E / Hylind, Linda M / Romans, Katharine / Griffin, Constance A / Cruz-Correa, Marcia / Giardiello, Francis M

Gut

2012 Volume 62, Issue 3, Page(s) 404–408

Abstract: Objective: Serrated (hyperplastic) polyposis (SP) is a rare disorder with multiple colorectal hyperplastic polyps and often sessile serrated adenomas/polyps (SSA/P) or adenomas. Although associated with colorectal cancer, the course of SP is not well ... ...

Abstract	Objective: Serrated (hyperplastic) polyposis (SP) is a rare disorder with multiple colorectal hyperplastic polyps and often sessile serrated adenomas/polyps (SSA/P) or adenomas. Although associated with colorectal cancer, the course of SP is not well described. Design: 44 patients with SP were studied. The results of 146 colonoscopies with median follow-up of 2.0 years (range 0-30) and a median of 1.0 years (range 0.5-6) between surveillance colonoscopies were evaluated. Findings from oesophogastroduodenoscopy examinations were analysed. Results: The mean age at diagnosis of SP was 52.5 ± 11.9 years (range 22-78). In two pedigrees (5%) another family member had SP. None of 22 patients had gastroduodenal polyps. All patients had additional colorectal polyps at surveillance colonoscopy. SSA/P or adenomas were found in 25 patients (61%) at first colonoscopy and 83% at last colonoscopy. Recurrent SSA/P or adenomas occurred in 68% of patients at surveillance colonoscopy. Three patients had colorectal cancer. Eleven patients (25%) underwent surgery (mean time from diagnosis of SP 2.0 ± 0.9 years). After surgery all seven surveyed patients developed recurrent polyps in the retained colorectum (4/7 had SSA/P or adenomas). No association was found between colorectal neoplasia and sex, age at diagnosis of SP or initial number of colorectal polyps. Conclusions: In SP, rapid and unrelenting colorectal neoplasia development continues in the intact colorectum and retained segment after surgery. These findings support the possibility of annual colonoscopic surveillance, consideration for colectomy when SSA/P or adenomas are encountered and frequent postoperative endoscopic surveillance of the retained colorectum.
MeSH term(s)	Adenoma/diagnosis ; Adenoma/genetics ; Adenoma/surgery ; Adult ; Aged ; Cell Transformation, Neoplastic ; Cohort Studies ; Colonic Polyps/pathology ; Colonic Polyps/surgery ; Colonoscopy ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/surgery ; Endoscopy, Gastrointestinal ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pedigree ; Precancerous Conditions ; Recurrence ; Registries ; Retrospective Studies ; Young Adult
Language	English
Publishing date	2012-04-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2011-300514
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Zs.A 160: Show issues

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Article ; Online: Risk of Colorectal and Other Cancers in Patients With Serrated Polyposis.

Edelstein, Daniel L / Cruz-Correa, Marcia / Soto-Salgado, Marievelisse / Axilbund, Jennifer E / Hylind, Linda M / Romans, Katharine / Blair, Cherie / Wiley, Elizabeth / Tersmette, Anne C / Offerhaus, Johan A / Giardiello, Francis M

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2015 Volume 13, Issue 9, Page(s) 1697–1699

Abstract: Patients with serrated polyposis develop multiple colorectal hyperplastic and/or serrated sessile adenomas/polyps. We investigated the risk of colorectal and other cancers by analyzing data from 64 patients with serrated polyposis (mean age at diagnosis, ...

Abstract	Patients with serrated polyposis develop multiple colorectal hyperplastic and/or serrated sessile adenomas/polyps. We investigated the risk of colorectal and other cancers by analyzing data from 64 patients with serrated polyposis (mean age at diagnosis, 54 y; 41% men; 92% white) listed in the Johns Hopkins Polyposis Registry. Medical, endoscopic, and histopathology reports were evaluated. Six patients (9.4%) had a history of colorectal cancer, diagnosed at a mean age of 56 years; 6 additional patients (9.4%) had at least 1 advanced colorectal adenoma. Extracolonic cancers were found in 16% of the study population. The standard incidence ratio for colorectal cancer in patients with serrated polyposis was 18.72 (95% confidence interval, 6.87-40.74) and for extracolonic cancer was 31.20 (95% confidence interval, 14.96-57.37), compared with the Surveillance, Epidemiology, and End Results population. Patients with serrated polyposis therefore have a high risk for colorectal cancer and require vigilant colorectal surveillance, starting at the time of diagnosis of serrated polyposis. The risk of extracolonic cancer also appears to be increased, but this requires further evaluation.
MeSH term(s)	Adenoma/epidemiology ; Adult ; Aged ; Cohort Studies ; Colonic Polyps/complications ; Colorectal Neoplasms/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Risk Assessment ; Young Adult
Language	English
Publishing date	2015-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2015.02.003
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Zs.A 5836: Show issues

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Article ; Online: Rapid development of colorectal neoplasia in patients with Lynch syndrome.

Edelstein, Daniel L / Axilbund, Jennifer / Baxter, Melanie / Hylind, Linda M / Romans, Katharine / Griffin, Constance A / Cruz-Correa, Marcia / Giardiello, Francis M

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2010 Volume 9, Issue 4, Page(s) 340–343

Abstract: Background & aims: Patients with Lynch syndrome have a high risk for colorectal adenomas and carcinomas. We evaluated the development of colorectal neoplasia in these patients.: Methods: We assessed serial colonoscopy findings from 54 persons from 29 ...

Abstract	Background & aims: Patients with Lynch syndrome have a high risk for colorectal adenomas and carcinomas. We evaluated the development of colorectal neoplasia in these patients. Methods: We assessed serial colonoscopy findings from 54 persons from 29 pedigrees with pathogenic mutations in MSH2 or MLH1; we evaluated the development of colorectal neoplasia by age, sex, tumor location, and number (mean follow-up time, 9.3 years; colonoscopy interval, 1.7 ± 1.2 years; 112 adenomas and 31 cancers). Differences in colorectal phenotype were analyzed by genotype, and dwell time was calculated for advanced neoplasias. Results: Among mutation carriers, the cumulative risk of colorectal neoplasia was 43% by age 40 years and 72% by 80 years. There were no statistically significant associations between time to development of colorectal neoplasia and sex or mutation type. Most female patients had left-sided neoplasms, whereas most male patients developed right-sided lesions. The mean cumulative numbers of neoplastic lesions in patients were 1.3 ± 0.5 by age 30 years and 7.6 ± 6.8 by age 80 years. Polyp dwell time was 33.0 ± 16.2 months and 35.2 ± 22.3 months for advanced adenoma and colorectal cancer, respectively. The 5-year survival rate for patients with colorectal cancer was 96%. Conclusions: High percentages of individuals with pathogenic mutations in MSH2 or MLH1 develop colorectal neoplasia by age 40. Left-sided colorectal neoplasias are more frequent in female patients. The development of 3 or more colorectal neoplasms by age 30 years indicates a possible polyposis syndrome rather than Lynch syndrome. Polyp dwell time is short for advanced neoplasias, arguing for annual colonoscopic screening and surveillance.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Colon/pathology ; Colonoscopy ; Colorectal Neoplasms, Hereditary Nonpolyposis/pathology ; Female ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein/genetics ; Mutation ; Nuclear Proteins/genetics ; Young Adult
Chemical Substances	Adaptor Proteins, Signal Transducing ; MLH1 protein, human ; Nuclear Proteins ; MSH2 protein, human (EC 3.6.1.3) ; MutL Protein Homolog 1 (EC 3.6.1.3) ; MutS Homolog 2 Protein (EC 3.6.1.3)
Language	English
Publishing date	2010-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2010.10.033
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Zs.A 5836: Show issues

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Article ; Online: Pre- and post-operative plasma glial fibrillary acidic protein levels in patients with newly diagnosed gliomas.

Husain, Hatim / Savage, William / Grossman, Stuart A / Ye, Xiaobu / Burger, Peter C / Everett, Allen / Bettegowda, Chetan / Diaz, Luis A / Blair, Cherie / Romans, Katharine E / Holdhoff, Matthias

Journal of neuro-oncology

2012 Volume 109, Issue 1, Page(s) 123–127

Abstract: Therapies that disrupt or repair blood-brain barrier integrity can result in major changes in MRI images even when the tumor volume remains constant. Thus, a reliable blood-based tumor biomarker could significantly improve clinical care and research ... ...

Abstract	Therapies that disrupt or repair blood-brain barrier integrity can result in major changes in MRI images even when the tumor volume remains constant. Thus, a reliable blood-based tumor biomarker could significantly improve clinical care and research studies in these patients. This study was performed to assess plasma concentrations of glial fibrillary acidic protein (GFAP) in patients with high- and low-grade gliomas before and after debulking surgery. Pre-operative plasma was collected from 33 patients with radiation- and chemotherapy-naïve gliomas. Additional plasma was collected 24-48 h post-operatively from 23 of these patients. Plasma GFAP (pGFAP) concentrations were determined using an electrochemiluminescent immunoassay and were analyzed as a function of tumor grade, tumor GFAP expression, the integrity of the blood-brain barrier, and post-operative status. Detectable pGFAP levels (≥ 0.04 ng/mL) were found pre-operatively in 52 % of patients and post-operatively in 96 %. Detectable pGFAP was more common in patients with WHO grade IV (100 %) than WHO grade III (56 %) or WHO grade II gliomas (20 %). No patient with undetectable GFAP had WHO grade IV glioma. Higher pGFAP concentrations were also associated with contrast enhancement but not related to tumor GFAP expression. GFAP is commonly detected in the plasma of patients with high-grade gliomas. pGFAP levels rise rather than fall following debulking surgery which is probably a result of surgical trauma. GFAP remains a potentially informative plasma biomarker for gliomas. Longitudinal studies are required to correlate pGFAP levels with patient outcomes.
MeSH term(s)	Adolescent ; Adult ; Aged ; Biomarkers, Tumor/blood ; Brain Neoplasms/blood ; Brain Neoplasms/diagnosis ; Brain Neoplasms/surgery ; Electrochemistry ; Female ; Glial Fibrillary Acidic Protein/blood ; Glioma/blood ; Glioma/diagnosis ; Glioma/surgery ; Humans ; Immunoenzyme Techniques ; Luminescent Measurements ; Male ; Middle Aged ; Neoplasm Grading ; Postoperative Period ; Prognosis ; Young Adult
Chemical Substances	Biomarkers, Tumor ; Glial Fibrillary Acidic Protein
Language	English
Publishing date	2012-04-11
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-012-0874-8
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Zs.A 1825: Show issues

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Article ; Online: Detection of tumor DNA at the margins of colorectal cancer liver metastasis.

Holdhoff, Matthias / Schmidt, Kerstin / Diehl, Frank / Aggrawal, Nishant / Angenendt, Philipp / Romans, Katharine / Edelstein, Daniel L / Torbenson, Michael / Kinzler, Kenneth W / Vogelstein, Bert / Choti, Michael A / Diaz, Luis A

Clinical cancer research : an official journal of the American Association for Cancer Research

2011 Volume 17, Issue 11, Page(s) 3551–3557

Abstract: Purpose: Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses.: ... ...

Abstract	Purpose: Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses. Experimental design: We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12, and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor. Results: Mutations were identified in each patient's resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in 5 of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA and of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor. Conclusions: Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases.
MeSH term(s)	Adult ; Aged ; Biopsy, Needle ; Class I Phosphatidylinositol 3-Kinases ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/surgery ; DNA, Neoplasm/analysis ; DNA, Neoplasm/genetics ; Female ; Genes, APC ; Genes, p53 ; Hepatectomy ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/secondary ; Liver Neoplasms/surgery ; Male ; Middle Aged ; Mutation ; Phosphatidylinositol 3-Kinases/genetics ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins/genetics
Chemical Substances	DNA, Neoplasm ; KRAS protein, human ; Proto-Oncogene Proteins ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CA protein, human (EC 2.7.1.137) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2011-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-10-3087
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Zs.A 4223: Show issues

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Article ; Online: A new phenotypic manifestation of familial adenomatous polyposis.

Edelstein, Daniel L / Giardiello, Francis M / Basiri, Ali / Hylind, Linda M / Romans, Katharine / Axilbund, Jennifer E / Cruz-Correa, Marcia / Ramella-Roman, Jessica C

Familial cancer

2011 Volume 10, Issue 2, Page(s) 309–313

Abstract: Familial adenomatous polyposis (FAP) is an autosomal dominant disease with hundreds of colorectal adenomas in teenagers and progression to colorectal cancer if colectomy is not performed. We investigated the association of two phenotypic manifestations- ... ...

Abstract	Familial adenomatous polyposis (FAP) is an autosomal dominant disease with hundreds of colorectal adenomas in teenagers and progression to colorectal cancer if colectomy is not performed. We investigated the association of two phenotypic manifestations-oral mucosal vascular density (OMVD) and oral mucosal reflectance (OMR)--with FAP and patients with multiple colorectal adenomas. Thirty-three patients with FAP from 29 unrelated pedigrees with APC gene mutation, 5 with multiple adenomas and no known gene mutations, and 50 population controls were evaluated for the two different manifestations utilizing a photographic/spectrophotometric system capturing images and reflectance at various wavelengths. Statistical analysis was performed with student t test and test performance characteristics were calculated. There were no significant differences in demographic variables between the FAP and control group. A significant difference in OMVD between FAP patients and controls was noted, P < 0.001. The sensitivity and specificity of oral mucosal vascular density for FAP was 91 and 90%, respectively. No association between this phenotypic manifestation and age or gender was found. All 5 patient with multiple polyps were positive for OMVD and the value was significantly higher than controls, P = 0.002. No significant difference was noted in OMR between the two patient groups and controls. OMVD is a new phenotypic manifestation in patients with FAP and also may identify those with multiple adenomas without known gene mutation.
MeSH term(s)	Adenomatous Polyposis Coli/complications ; Adult ; Female ; Humans ; Male ; Middle Aged ; Mouth Mucosa/blood supply ; Mouth Mucosa/pathology ; Phenotype ; Vascular Endothelial Growth Factor A/analysis
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2011-03-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1502496-9
ISSN	1573-7292 ; 1389-9600
ISSN (online)	1573-7292
ISSN	1389-9600
DOI	10.1007/s10689-011-9432-3
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Zs.A 6099: Show issues

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Article ; Online: Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution.

Genome research

2015 Volume 25, Issue 10, Page(s) 1536–1545

Abstract: Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), ...

Abstract	Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds, and many were present in multiple tumor sections, implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth.
MeSH term(s)	Disease Progression ; Gastrointestinal Neoplasms/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Long Interspersed Nucleotide Elements ; Mutagenesis, Insertional ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics ; Oligonucleotide Array Sequence Analysis ; Time Factors
Chemical Substances	Neoplasm Proteins
Language	English
Publishing date	2015-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.196238.115
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Zs.A 3729: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Occurrence of colorectal adenomas in younger adults: an epidemiologic necropsy study.

Pendergrass, Cheryl J / Edelstein, Daniel L / Hylind, Linda M / Phillips, Blaine T / Iacobuzio-Donahue, Christine / Romans, Katharine / Griffin, Constance A / Cruz-Correa, Marcia / Tersmette, Anne C / Offerhaus, G Johan A / Giardiello, Francis M

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2008 Volume 6, Issue 9, Page(s) 1011–1015

Abstract: Background & aims: The colorectal adenoma is the precursor lesion in virtually all colorectal cancers. Occurrence of colorectal adenomas has been studied in older adults but analysis in younger adults is lacking.: Methods: The prevalence by age, sex, ...

Abstract	Background & aims: The colorectal adenoma is the precursor lesion in virtually all colorectal cancers. Occurrence of colorectal adenomas has been studied in older adults but analysis in younger adults is lacking. Methods: The prevalence by age, sex, race, and location, and the number of colorectal adenomas detected was investigated using epidemiologic necropsy in 3558 persons ages 20 to 89 autopsied from 1985 to 2004 at the Johns Hopkins Hospital. Results were standardized to the general population. Younger adults 20 to 49 years old were compared with older adults 50 to 89 years old. Results: The prevalence of colorectal adenomas in younger adults increased from 1.72% to 3.59% from the third to the fifth decade of life and then sharply increased after age 50. In younger adults, adenomas were more prevalent in men than in women (risk ratio, 1.09; 95% confidence interval, 1.07-1.11) and in whites than in blacks (risk ratio, 1.28; 95% confidence interval, 1.26-1.31). Overall, both younger and older adults had predominately left-sided adenomas, but blacks in both age groups had more right-sided adenomas. Occurrence of 2 or more adenomas in younger adults and 5 or more in older adults was greater than 2 SDs from the mean. Conclusions: Colorectal adenomas infrequently occur in younger adults and are more prevalent in the left colon. Irrespective of age, blacks have more right-sided adenomas, suggesting the need for screening the entire colorectum. Two or more adenomas in younger adults and 5 or more in older adults represents polyp burden outside the normal expectation.
MeSH term(s)	Adenoma/epidemiology ; Adult ; Aged ; Aged, 80 and over ; Colon, Descending ; Colorectal Neoplasms/epidemiology ; Continental Population Groups ; Female ; Humans ; Male ; Maryland/epidemiology ; Middle Aged ; Prevalence ; Risk Factors ; Sex Factors
Language	English
Publishing date	2008-06-16
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2008.03.022
Database	MEDical Literature Analysis and Retrieval System OnLINE

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