Deep sequencing of the X chromosome reveals the proliferation history of colorectal adenomas

Table 1 Sample description

Sample	Age (years)	Germline mutation	Tumor histology	MMR immunohistochemistry	MSI		BRAF somatic mutations^b	KRAS somatic mutations^c	Other somatic modifications
Sample	Age (years)	Germline mutation	Tumor histology	MMR immunohistochemistry	Unstable/Total	Markers	BRAF somatic mutations^b	KRAS somatic mutations^c	Other somatic modifications
A1	44	MSH2: c.(?_-68)_792 + ?del (deletion of exons 1 to 4)	Low-grade tubular adenoma with focal high-grade dysplasia, ≥50% tumor content^a	Loss of MSH2	5	BAT25, BAT26, NR21, NR24, MONO-27	Wild type	Wild type	-
A2	50	MSH2: c.2738delC	Flat adenoma with low to high dysplasia	Loss of MSH2	3	BAT26 (minor fraction), NR21, MONO-27	Wild type	Wild type	-
A3	77	-	85% well differentiated, early adenocarcinoma with up to severe dysplasia	Loss of MLH1	4	BAT26, BAT25, NR24, MONO-27	V600E	Wild type	MLH1 hypermethylation
A4	48	MSH2: c.1216C > T	60% adenomatous tissue, 25% well-differentiated adenocarcinoma extending into the muscular layer	Loss of MSH2	4	BAT26, NR21, NR24, MONO-27	Wild type	Wild type	-

For each sample, age at the time of tumor resection, germline mutation, tumor histology, immunohistochemistry of mismatch repair (MMR) proteins, measure of microsatellite instability (MSI), and somatic mutation in colorectal cancer hotspots are reported. Germline mutations are described according to the Human Genome Variation Society (http://www.hgvs.org/mutnomen). MSI was assessed by checking for a panel of five unstable microsatellite markers (BAT25, BAT26, NR21, NR24, and MONO-27).
^aTumor content was inferred from the MSI spectrum [26].
^bMutation V600E was screened by TaqMan assay in samples A2, A3, A4 and by direct sequencing of BRAF exon 15 in sample A1.
^cKRAS exons 2 and 3 were sequenced in all samples, except for sample A1 where only exon 2 was screened.

ISSN: 1474-760X