Volume 126, Issue 2, Pages (February 2004)

Slides:

Advertisements

Similar presentations

Diffuse Type Gastric and Lobular Breast Carcinoma in a Familial Gastric Cancer Patient with an E-Cadherin Germline Mutation Gisela Keller, Holger Vogelsang,

Advertisements

Matthew D. Rutter, Robert H. Riddell

Germline and Somatic Mutations of the STK11/LKB1 Peutz-Jeghers Gene in Pancreatic and Biliary Cancers Gloria H. Su, Ralph H. Hruban, Ravi K. Bansal,

Volume 50, Issue 5, Pages (November 2006)

Tumor Microsatellite Instability in Early Onset Gastric Cancer

Epidermolysis Bullosa: Novel and De Novo Premature Termination Codon and Deletion Mutations in the Plectin Gene Predict Late-Onset Muscular Dystrophy

Molecular Diagnosis of Epstein-Barr Virus-Related Diseases

Preinvasive Neoplasia in the Stomach: Diagnosis and Treatment

Volume 119, Issue 4, Pages (October 2000)

Volume 50, Issue 5, Pages (November 2006)

Extensive but hemiallelic methylation of the hMLH1 promoter region in early-onset sporadic colon cancers with microsatellite instability Yasuyuki Miyakura,

Carcinogenesis of Helicobacter pylori

Volume 126, Issue 1, Pages (January 2004)

Volume 133, Issue 6, Pages (December 2007)

Volume 119, Issue 4, Pages (October 2000)

Virtual Histology in Everyday Gastrointestinal Endoscopy

Volume 116, Issue 2, Pages (February 1999)

KRAS, NRAS, PIK3CA Exon 20, and BRAF Genotypes in Synchronous and Metachronous Primary Colorectal Cancers Katharina Balschun, Jochen Haag, Ann-Kathrin.

Somatic mutations in mitochondrial DNA do not associate with nuclear microsatellite instability in gastrointestinal cancer Simó Schwartz, M.D., Ph.D.*,†,

Total-Genome Analysis of BRCA1/2-Related Invasive Carcinomas of the Breast Identifies Tumor Stroma as Potential Landscaper for Neoplastic Initiation

Volume 129, Issue 5, Pages (November 2005)

Molecular Validation of the Modified Vienna Classification of Colorectal Tumors Tamotsu Sugai, Wataru Habano, Noriyuki Uesugi, Yu-Fei Jiao, Shin-ichi.

Volume 138, Issue 2, Pages (February 2010)

Volume 124, Issue 5, Pages (May 2003)

Genetic testing for high-risk colon cancer patients1

Volume 129, Issue 6, Pages (December 2005)

Karin D. Berg, Cynthia L. Glaser, Richard E. Thompson, Stanley R

Volume 63, Issue 1, Pages (January 2003)

Volume 140, Issue 1, Pages e5 (January 2011)

Detection of KRAS and BRAF Mutations in Colorectal Carcinoma

A Novel Alu-Like Element Rearranged in the Dystrophin Gene Causes a Splicing Mutation in a Family with X-Linked Dilated Cardiomyopathy Alessandra Ferlini,

Volume 128, Issue 4, Pages (April 2005)

Volume 118, Issue 5, Pages (May 2000)

Volume 141, Issue 1, Pages e23-e26 (July 2011)

Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto

Matthew D. Rutter, Robert H. Riddell

Wide-area transepithelial sampling with 3-dimensional cytology: Does it detect more dysplasia or yield more hype? Marcia Irene Canto, MD, MHS Gastrointestinal.

Volume 124, Issue 3, Pages (March 2003)

Complement Factor H Gene Mutation Associated with Autosomal Recessive Atypical Hemolytic Uremic Syndrome Lihua Ying, Yitzhak Katz, Menachem Schlesinger,

Epidermolysis Bullosa: Novel and De Novo Premature Termination Codon and Deletion Mutations in the Plectin Gene Predict Late-Onset Muscular Dystrophy

Association of Hereditary Nonpolyposis Colorectal Cancer–Related Tumors Displaying Low Microsatellite Instability with MSH6 Germline Mutations Ying Wu,

Microsatellite Instability in Colorectal Cancer

Germline Mutation of INI1/SMARCB1 in Familial Schwannomatosis

Novel SLC39A4 Mutations in Acrodermatitis Enteropathica

Challenges and Pitfalls in HNPCC Screening by Microsatellite Analysis and Immunohistochemistry Annegret Müller, Giuseppe Giuffre, Tina Bocker Edmonston,

Survival of Male Patients with Incontinentia Pigmenti Carrying a Lethal Mutation Can Be Explained by Somatic Mosaicism or Klinefelter Syndrome The.

Activation of a Cryptic Splice Site of PTEN and Loss of Heterozygosity in Benign Skin Lesions in Cowden Disease Stephen J. Meltzer, Manfred Wolter Journal.

Molecular Diagnosis of Metastasizing Oligodendroglioma

Mark L. Kayton, MD, Mai He, MD, PhD, Maureen F. Zakowski, MD, Andre L

The Neurofibromatosis Type 1 (Nf1) Tumor Suppressor is a Modifier of Carcinogen- Induced Pigmentation and Papilloma Formation in C57BL/6 Mice Radhika.

Volume 128, Issue 2, Pages (February 2005)

Volume 145, Issue 1, Pages (July 2013)

AGA Technical Review on the Diagnosis and Management of Colorectal Neoplasia in Inflammatory Bowel Disease Francis A. Farraye, Robert D. Odze, Jayne.

Volume 128, Issue 5, Pages (May 2005)

The role of sequence variations within the genes encoding collagen II, IX and XI in non- syndromic, early-onset osteoarthritis E. Jakkula, M.D., M. Melkoniemi,

Germline Epigenetic Silencing of the Tumor Suppressor Gene PTPRJ in Early-Onset Familial Colorectal Cancer Ramprasath Venkatachalam Gastroenterology

A Missense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia in a Family of Irish Travellers Wasim Ahmad, Alan.

A Novel Point Mutation Affecting the Tyrosine Kinase Domain of the TRKA Gene in a Family with Congenital Insensitivity to Pain with Anhidrosis Shinichi.

Volume 130, Issue 7, Pages (June 2006)

Volume 126, Issue 3, Pages (March 2004)

Colorectal cancer at a young age

A B C D G G/A Figure 1. Sequencing reveals mosaicism for point mutation. A. Sequencing shows a homozygous c.862 G>A mutation in the DNA from tumor of unilaterally.

Gabriella Esposito, Giuseppe Rescigno, Francesco Salvatore

Masahide Yazaki, Sandra A. Farrell, Merrill D. Benson

Volume 71, Issue 6, Pages (March 2007)

Volume 53, Issue 5, Pages (May 1998)

Mutations in CHEK2 Associated with Prostate Cancer Risk

Identification of a New Gene Locus for Adolescent Nephronophthisis, on Chromosome 3q22 in a Large Venezuelan Pedigree Heymut Omran, Carmen Fernandez,

Volume 92, Issue 5, Pages (March 1998)

Volume 125, Issue 2, Pages (August 2003)

Presentation transcript:

Volume 126, Issue 2, Pages 576-585 (February 2004) Gastrointestinal cancers and neurofibromatosis type 1 features in children with a germline homozygous MLH1 mutation Steven Gallinger, Melyssa Aronson, Katayoon Shayan, Elyanne M. Ratcliffe, Justin T. Gerstle, Patricia C. Parkin, Heidi Rothenmund, Marina Croitoru, Ewa Baumann, Peter R. Durie, Rosanna Weksberg, Aaron Pollett, Robert H. Riddell, Bo Y. Ngan, Ernest Cutz, Alain E. Lagarde, Helen S.L. Chan Gastroenterology Volume 126, Issue 2, Pages 576-585 (February 2004) DOI: 10.1053/j.gastro.2003.11.008

Figure 1 Pedigree of this HNPCC family showing 4 generations (I-IV), with relevant individuals in each generation indicated by numbers on the top right corner of the symbols. Males are indicated by squares and females by circles. Double lines indicate a consanguineous union. Family members with reported or confirmed cancers are shown in black. Their ages at diagnosis are indicated below the symbols. Diagonal lines indicate deceased individuals with age of death (d) shown. Numbers within the symbols indicate the numbers of unaffected siblings. NF1, features of neurofibromatosis. Gastroenterology 2004 126, 576-585DOI: (10.1053/j.gastro.2003.11.008)

Figure 2 Low-power view of the proband’s duodenal biopsy sample; the infiltrating adenocarcinoma forms small back-to-back glands (arrow). Glands close to the surface show adenomatous changes (arrowhead; stain, hematoxylin and eosin; magnification, 100×). The inset shows a close-up of stromal invasion (stain, hematoxylin and eosin; magnification, 400×). Gastroenterology 2004 126, 576-585DOI: (10.1053/j.gastro.2003.11.008)

Figure 3 (A) Low-power view of a colon polyp from child 2 showing the region of invasive adenocarcinoma. The adenocarcinomas had a cribriform architecture with loss of polarity and increased nuclear size. The nuclei were rounded, with prominent nucleoli. Increased abnormal mitotic figures and areas of necrosis were present. Most of the glands were dysplastic with crowding large, and dilated glands had pools of mucin in their centers (stain, hematoxylin and eosin; magnification, 16×). (B) High-power view showing stromal invasion and malignant nuclear features (stain, hematoxylin and eosin; magnification, 400×). Gastroenterology 2004 126, 576-585DOI: (10.1053/j.gastro.2003.11.008)

Figure 4 (A) MSH2 immunohistochemical staining showing nuclear staining in the normal (right) and dysplastic (left) epithelium of the malignant colon polyps from child 2. Scattered staining in lymphocytes within the lamina propria can also be seen. MSH6 showed a similar pattern (not shown; MSH2, 250×). (B) MLH1 immunohistochemical staining of the tumor showed weak nuclear staining in the adenomatous and malignant epithelium. Similar MLH1 staining was seen in all lesions (MLH1, 400×). (C) The normal epithelium and germinal centers also showed weak nuclear staining, similar to the pattern seen in the tumors (MLH1, 400×). Gastroenterology 2004 126, 576-585DOI: (10.1053/j.gastro.2003.11.008)

Figure 5 High-frequency microsatellite instability (MSI-H) in metastatic duodenal adenocarcinoma from the proband (IV-1) and in all 3 malignant colon polyps from his sister (child 2; IV-2). An autoradiograph with the BAT26 mononucleotide marker is shown. Note the shifted band patterns (arrows) in the lanes with DNA from the duodenal cancer and the colon polyps compared with the paired normal mucosa. DT, metastatic duodenal tumor; DN, normal duodenum; P, polyps; CN, normal colon. Gastroenterology 2004 126, 576-585DOI: (10.1053/j.gastro.2003.11.008)

Figure 6 Enlarged section of the pedigree shown in Figure 1 with sequencing images in the region comprising codon 687 in exon 18 of the MLH1 gene. The normal codon (CCG) is Arg, and the mutant codon (CCA) is Trp (note that reverse sequencing is shown). Both parents (III-1 and III-2) are Arg687Trp heterozygotes, and all 3 children (IV-1, IV-2, and IV-3) are Arg687Trp homozygotes. Gastroenterology 2004 126, 576-585DOI: (10.1053/j.gastro.2003.11.008)

Figure 7 Microsatellite instability in lymphoblasts in a child with a homozygous MLH1 Arg687Trp mutation. A dilutional PCR assay was performed with amplification of DNA extracted from Epstein-Barr virus-transformed lymphoblasts. Microsatellite alleles diluted to approximately single copies are shown. Note the shifted band patterns (arrows) in some of the PCR products from child 3 (IV-3 in the pedigree) compared with those from her mother (III-2), which are stable. Similar patterns were seen in samples from the other 2 affected children (IV-1 and IV-2). Gastroenterology 2004 126, 576-585DOI: (10.1053/j.gastro.2003.11.008)