FaCD Online Syndrome Fact Sheet

Last updated: 28 Nov 2011

Name: MSI-Stable Early-Onset & Familial Colorectal Cancer

Synonym: incl. Familial Colorectal Cancer type X

Mode of Inheritance: AD? /multifact?


PTPRJ, mapped to 11p11.2

Tumor features

colorectal cancer


Lindor et al[1] coined the name Familial Colorectal Cancer type X for those families that meet the Lynch syndrome clinical criteria but do not show mismatch repair deficiency. Relatives in such families showed a lower incidence of colorectal cancer than those in families with Lynch syndrome.

In general, MSI-low/stable early-onset and/or familial colorectal cancer, is expected to be a heterogenous group, with reported associated CNVs, epigenetic silencing of PTPRJ and a range of other germline variants and loci involved[2-5]. Francisco et al[6] have identified two different subgroups within a Familial Colorectal Cancer type X cohort of 15 families: one whose tumours present frequent loss of tumor suppressor genes APC, TP53, SMAD4 and DCC, APC and KRAS somatic mutations, and MGMT promoter methylation, and a second, lesser predominant type, with no evidence of tumor supperessor gene loss and rarely presenting promoter methylation.


[1] Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, Gallinger S, Bapat B, Aronson M, Hopper J, Jass J, LeMarchand L, Grove J, Potter J, Newcomb P, Terdiman JP, Conrad P, Moslein G, Goldberg R, Ziogas A, Anton-Culver H, de Andrade M, Siegmund K, Thibodeau SN, Boardman LA, Seminara D. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA : the journal of the American Medical Association 2005; 293(16):1979-85.
[2] Venkatachalam R, Verwiel ET, Kamping EJ, Hoenselaar E, Görgens H, Schackert HK, van Krieken JH, Ligtenberg MJ, Hoogerbrugge N, van Kessel AG, Kuiper RP. Identification of candidate predisposing copy number variants in familial and early-onset colorectal cancer patients. Int J Cancer. 2011 Oct 1;129(7):1635-42.
[3] Venkatachalam R, Ligtenberg MJ, Hoogerbrugge N, Schackert HK, Görgens H, Hahn MM, Kamping EJ, Vreede L, Hoenselaar E, van der Looij E, Goossens M, Churchman M, Carvajal-Carmona L, Tomlinson IP, de Bruijn DR, Van Kessel AG, Kuiper RP. Germline epigenetic silencing of the tumor suppressor gene PTPRJ in early-onset familial colorectal cancer. Gastroenterology. 2010 Dec;139(6):2221-4.
[4] Gylfe AE, Sirkiä J, Ahlsten M, Järvinen H, Mecklin JP, Karhu A, Aaltonen LA. Somatic mutations and germline sequence variants in patients with familial colorectal cancer.Int J Cancer. 2010 Jun 29. [Epub ahead of print]
[5] Skoglund J, Djureinovic T, Zhou XL, Vandrovcova J, Renkonen E, Iselius L, Bisgaard ML, Peltomäki P, Lindblom A. Linkage analysis in a large Swedish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 9q22.32-31.1. J Med Genet. 2006 Feb;43(2):e7.
[6] Francisco I, Albuquerque C, Lage P, Belo H, Vitoriano I, Filipe B, Claro I, Ferreira S, Rodrigues P, Chaves P, Leitão CN, Pereira AD. Familial colorectal cancer type X syndrome: two distinct molecular entities? Fam Cancer. 2011 Aug 12. [Epub ahead of print]