Volume 122, Issue 5, Pages 1493-1499 (May 2002) Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene  Seiichi Hirota, Toshirou Nishida, Koji Isozaki, Masahiko Taniguchi, Kazuhiro Nishikawa, Akiko Ohashi, Arimichi Takabayashi, Tadashi Obayashi, Tomoko Okuno, Kazuo Kinoshita, Hui Chen, Yasuhisa Shinomura, Yukihiko Kitamura  Gastroenterology  Volume 122, Issue 5, Pages 1493-1499 (May 2002) DOI: 10.1053/gast.2002.33024 Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 1 Pedigree of the family. Filled symbols showed the family members with both KIT mutation and GISTs. Case 2 died from a large abdominal tumor without operation. Squares and circles show male and female cases, respectively. Slashes indicate dead cases at the time of investigation. Gastroenterology 2002 122, 1493-1499DOI: (10.1053/gast.2002.33024) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 2 (A and B) Immunohistochemical characteristics of the tumor and (C and D) hyperplastic spindle-shaped cells in the myenteric plexus layer of the small intestine of case 4. A and C were stained with anti-KIT antibody, and B and D were stained with anti-CD34 antibody. Both the tumor and hyperplastic spindle-shaped cells in the myenteric plexus layer were positive for KIT and CD34. CM, circular muscle layer; LM, longitudinal muscle layer; MP, myenteric plexus layer. Gastroenterology 2002 122, 1493-1499DOI: (10.1053/gast.2002.33024) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 3 Autonomous proliferation of Ba/F3 cells with KIT-D820Y in culture and nude mice. KIT-D820Y was transfected into Ba/F3 cells. Mouse wild-type KIT cDNA and KIT-del559-560 were transfected as controls. MTT colorimetric assay in the presence or absence of (A) rmIL-3 and (B) rmSCF. Data are expressed as the mean of 4 wells. (C) Development of tumors in nude mice after injection of various Ba/F3 cells. Ba/F3 cells with KIT-D820Y showed factor-independent growth and formed tumors. ○, untransfected Ba/F3 cells; ■, Ba/F3 cells with the wild KIT; □, Ba/F3 cells with KIT-del559-560; ●, Ba/F3 cells with KIT-D820Y. Gastroenterology 2002 122, 1493-1499DOI: (10.1053/gast.2002.33024) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 4 Representative EUS images at the esophagocardiac junction. (A) A thin hyperechoic layer was detectable between the circular and longitudinal muscle layers in a normal control. (B) The hyperechoic layer apparently thickened in case 6. Arrowheads indicate the hyperechoic layer between the circular and longitudinal muscle layers. Gastroenterology 2002 122, 1493-1499DOI: (10.1053/gast.2002.33024) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 5 Representative profiles of esophageal manometry in case 8. No peristalsis was detected in the esophageal body, but simultaneous contractions with low amplitude were observed. The resting LES pressure was lower than the pressure reported in patients with typical achalasia. Recording sites of 1, 2, 3, 4, 5, 6, and 8 correspond to 29, 15, 12, 9, 6, 3, and −4 cm relative to the center of the sleeve (7). WS, wet swallowing; DS, dry swallowing. Gastroenterology 2002 122, 1493-1499DOI: (10.1053/gast.2002.33024) Copyright © 2002 American Gastroenterological Association Terms and Conditions