Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

Table 3 Germline LGRs identified in Slovakian HNPCC families.

Family code	HNPCC criteria	Tumor localization (age at diagnosis)	Gene	Deleted or duplicated exons (systematic nomenclature)	5' deletion	MSI	IHC	LOH
SK-14	AC-I	ascendens + sigmoid colon (27)	MSH2	del1-7 (c.1-?_1276+?del)	15 kb	MSI-H	*	partial
SK-20	AC-II	sigmoid colon (36)	MSH2	dup5-6 (c.793-?_1076+?dup)	n.a.	MSI-H	MLH1⁺, MSH2^-	partial
SK-21	BG	cecum (27)	MSH2	del1-3 (c.1-?_645+?del)	15 kb and 27 kb	MSI-H	MLH1⁺, MSH2^-	none
SK-22	AC-I	sigmoid colon (36)	MLH1	del5-6 (c.381-?_545+?del)	n.a.	MSI-H	MLH1^-, MSH2⁺	partial
SK-23	AC-I	cecum + ascendens colon (53)	MSH2	del1 (c.1-?_211+?del)	-	MSI-L	*	none
SK-25	AC-I	cecum (42)	MSH2	del1-7 (c.1-?_1276+?del)	15 kb	#	#
SK-28	BG	ascendens colon + rectum (48)	MSH2	del1-3 (c.1-?_645+?del)	n.d.	MSI-H	*	n.i.

Fulfillment of HNPCC criteria: AC-I, AC-II, Amsterdam criteria I, II; BG, Bethesda guidelines. Systematic nomenclature: According to the recommendations of the Human Genome Variant Society using reference sequences NM_000249.2 (MLH1) and NM_000251.1 (MSH2). 5' deletion: the probes detecting regions located 15 or 27 kb before MSH2 localized in the TACSTD1 gene; n.a., not applicable; - no reduction of the signal at any of the TACSTD1 probes, n.d., not determined; MSI, microsatellite instability analysis: MSI-H, high level of MSI; MSI-L, low level of MSI; IHC, immunohistochemical analysis, ⁺, a positive staining, ^-, a negative staining, * staining failed due to fixation problem; #, no FFPE tissue available for analysis; LOH, loss of heterozygosity, n.i. not informative in any LOH marker

ISSN: 1471-2407