22 November 1993; accepted 24 January 1994 on May 20, 2014 on May 20, 2014 on May 20, 2014 on May 20, 2014 on May 20, 2014 www.sciencemag.org www.sciencemag.org www.sciencemag.org www.sciencemag.org www.sciencemag.org Mutation of a mutL Homolog in Hereditary Colon Cancer Nickolas Papadopoulos,* Nicholas C. Nicolaides,* Ying-Fei Wei, Steven M. Ruben, Kenneth C. Carter, Craig A. Rosen, William A. Haseltine, Robert D. Fleischmann, Claire M. Fraser, Mark D. Adams, J. Craig Venter, Stanley R. Hamilton, Gloria M. Petersen, Patrice Watson, Henry T. Lynch, Paivi Peltomaki, Jukka-Pekka Mecklin, Albert de la Chapelle, Kenneth W. Kinzler,f Bert Vogelstein Some cases of hereditary nonpolyposis colorectal cancer (HNPCC) are due to alterations in a mutS-related mismatch repair gene.
We determined the conversion rate for each in- sertion site by crossing males bearing the whd allele [whdtk17 in previous work (20)], one copy of P[walter], and the A2-3 transposase source (14) with C(1)DX,y ffemales (21) and scoring the progeny as described (9).
In addition, EST sequencing, Northern (RNA) blots, and RT-PCR analyses showed that the hMLHI gene is expressed in many tissues lymphocytes, including breast, colon, lung, spleen, testes, prostate, thyroid, gall bladder, and heart, in keeping with its presumptive housekeeping function.
Each of these kindreds met the International Collabora- tive Group criteria for HNPCC [three fam- ily members affected with colorectal cancer, at least two generations involved, at least one patient under 50 years of age at diag- nosis (26)].
Supported by the Clayton Fund, the Folkhasan Institute of Genetics, the Academy of Finland, the Sigrid Juselius Foundation, the Nebraska State Health Department of Cancer, the Council for Tobacco Research, and NIH grants CA35494, CA47527, and CA57435.