CASE REPORTS Using Genetic Information to Make Surgical Decisions Report of a Cancer Lisa Madlensky, Rick Pearl, M.D.,} Steve Gallinger, M.D.,*$ Zane Cohen, M.D.*~ From the *Steve Atanas Stavro Familial GI Cancer Registry, Mount Sinai Hospital, the Departments of tPathology and $Surgery, Mount Sinai Hospital and the #Hospital for Sick Children, Toronto, University of Toronto, Toronto, Ontario, Canada Case of a 13-Year-Old Boy with Colon M.Sc.,* Bharati Bapat, Ph.D.,*t Mark Redston, M.D.,*t PURPOSE: We report the case of a boy aged 13 years who was diagnosed with a Dukes B obstructing cancer of the sigmoid colon. At the time of diagnosis, he underwent a Hartmann's procedure with end colostomy. Because of his unusually young age, he was referred to the Familial GI Cancer Registry at Mount Sinai Hospital for genetic assess- ment. A detailed pedigree revealed no significant history other than lung cancer in his maternal grandfather. METH- ODS: We obtained his tumor specimen and performed mo- lecular analysis of both normal colonic and tumor DNA. Specifically, we identified replication errors (RER) in the patient's tumor DNA when compared with normal colonic DNA. RER has been found in more than 90 percent of tumors from patients with Hereditary Nonpolyposis Colon Cancer (HNPCC) and is, thus, considered to be one of the hallmarks of this disease. Because HNPCC patients have a 40 percent risk of synchronous or metachronous tumors, the recommended surgery for HNPCC should be at least a subtotal colectomy with ileorectal anastomosis. RESULTS: Based on molecular results, we were able to recommend that the patient have a subtotal colectomy performed in- stead of merely colostomy closure, to reduce his lifetime risk of developing further colon tumors and to make sur- veillance of the remaining rectum relatively easy. In this patient, we subsequently identified a gerufline mutation of the mismatch repair gene hMSH2 that is implicated in HNPCC. The possibility of HNPCC should be considered in adolescents who are diagnosed with colorectal cancer, so appropriate surgical decisions can be made. [Key words: Hereditary nonpolyposis colorectal carcinoma; Microsatel- lite instability; Genetic counseling; Registries] Madlensky L, Bapat B, Redston M, Pearl R, Gallinger S, Cohen Z. Using genetic information to make surgical deci- sions: report of a case of a 13-year-old boy with colon cancer. Dis Colon Rectum 1997;40:240-243. Read at the annual meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996. Address reprint requests to Ms. Madlensky: Suite 1159 Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G lX5. A denocarcinoma of the colon is very rare in ado- lescents. The survival rate for this group of pa- tients is relatively low, presumably because there is often a delay in diagnosis.l-5 Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic condition that predisposes affected individuals to the development of colon and other cancers at a younger age than the general population. The average age of colon cancer diagnosis in the United States is in the mid 60s, and in patients with HNPCC it is 44. 6, 7 Several cases of colon cancer in adolescents have been reported in HNPCC, both with and without family histories of cancer, s-l~ A diagnosis of HNPCC can be made in one of two ways: by family history or by molecular techniques that identify a causative HNPCC gene mutation in an affected individual and/or family. Diagnosing HNPCC by family history is usually done using the "Amster- dam criteria, ''I1 which include 1) three individuals affected with colon cancer in two successive genera- tions; 2) one of the individuals is under the age of 50 years; 3) one of the individuals is a first-degree rela- tive of the other two; 4) familial adenomatous polyp- osis (FAP) is excluded. Using molecular techniques, putative HNPCC patients are screened for germline mutations in the MSH2, MLH1, PMS1, and PMS2 genes, which are known to cause HNPCC. 12-16 These genes code for proteins that are part of the DNA mismatch repair pathway that ensures fidelity of DNA replication during the normal cell cycle. 17 One of the hallmarks of HNPCC is the presence of replication errors (RER) or microsatellite instability in tumor DNA. 18-2~ Microsatellites are short, repetitive sequences of DNA distributed throughout the ge- 240