Online Supplement, Tables S1 through S4

Table S1. Current Procedural Terminology (CPT) codes used to identify records of screening colonoscopies performed at a University of Utah Healthcare facility, 2000-2012.

CPT code / Definition
45355 / Surgical colonoscopy
45378 / Diagnostic colonoscopy
45380 / Colonoscopy with biopsy
45381 / Colonoscopy, submucosal injection
45382 / Colonoscopy, bleeding control
45383, 45384, 45385 / Lesion removal colonoscopy
G0105, G0121 / Medicare-reimbursed colonoscopy screening

Table S2. Example of source data, University of Utah Healthcare endoscopy report.

Procedure: After I obtained informed consent, the scope was passed

under direct vision. ASA class P2 Throughout the procedure,

the patient's blood pressure, pulse, and oxygen saturations

were monitored continuously. The Colonoscope was introduced

through the anus and advanced to the cecum, identified by

appendiceal orifice \E&E\ IC valve. The colonoscopy was

accomplished without difficulty. The patient tolerated the

procedure well. The quality of the prep was good.

Findings: A sessile polyp was found in the ascending colon. The polyp

was 7 mm in size. Polypectomy was performed with a cold

forceps. Resection and retrieval were complete. Internal

hemorrhoids were found.

Impression: - One 7 mm polyp in the ascending colon. Resected and

retrieved.

Table S3. Example of source data, University of Utah Healthcare surgical pathology report.

SP DIAGNOSIS: 1. COLON, BIOPSY ASCENDING POLYP: - HYPERPLASTIC POLYP \

------04/15/05I certify that I personally conducted the diagnosticevaluation on the above specimen(s) and have rendered the above diagnosis(es): ______, M.D. electronic signature

SP COMMENTS: "

Online Supplement, continued

Table S4. Example of endoscopy exclusion criteria search terms applied to concatenated sentence fields (procedure, findings, and impression) using Microsoft SQL (2005). The operator ‘%’ indicates any text preceding or appearing after the search term; lower-case and upper-case text matching the specified string is returned.

Text indication that entire colon was not examined or bowel preparation was incomplete:

SELECT Report_ID INTO #PREP FROM #SOURCE_TBL WHERE

(

IMPRESSION LIKE '%stool%'

OR IMPRESSION LIKE '%aborted%'

OR (IMPRESSION LIKE '%poor%' and IMPRESSION LIKE '%prep%')

OR (IMPRESSION LIKE '%incomplete%' and IMPRESSION LIKE '%prep%')

OR (IMPRESSION LIKE '%inadequate%' and IMPRESSION LIKE '%prep%')

OR (IMPRESSION LIKE '%not satisf%' and IMPRESSION LIKE '%prep%')

)

Text indicating ulcerative colitis/irritable bowel disorder or diverticula:

SELECT Report_ID INTO #UC FROM #SOURCE_TBL WHERE

(

IMPRESSION LIKE '%diverticul%'

OR IMPRESSION LIKE '%colitis%'

OR IMPRESSION LIKE '%ulcer%'

OR IMPRESSION LIKE '%inflam%'

OR IMPRESSION LIKE '%irrita%'

)

Sequenom Protocol

The polypoid epithelium from 93 samples was specified by a pathologist and sent for DNA isolation and Sequenom somatic mutation profiling. The formalin fixed paraffin embedded (FFPE) specimens were cut at 5 µm and at total of 2-8 sections were stained with aniline blue. Sections were manually microdissected using the circled H&E as a template. DNA was extracted using QlAamp DNA FFPE Tissue Kit (Qiagen) following the standard protocol. DNA yields were determined using a NanoDrop 8000 (ThermoScientific). Samples were normalized to a DNA concentration of 10 ng/µL in TE. Somatic mutations in BRAF codon 600, KRAS codons 12, 13, 61, and 146, NRAS codons 12, 13, and 61, and PIK3CA codons 542, 545, and 1047 were detected using the SequenomMassArray. Briefly, multiplexed PCR was initially performed utilizing Sequenom’siPlexPro chemistry. The PCR contained: 0.8 µL H2O (molecular biology grade), 0.5 µL PCR buffer, 0.4 µL 25 mM MgCl2, 0.1 µL 25 mM dNTPs, 0.2 µL PCR enzyme (5 U/µL), 1 µL multiplexed primer mix, and 2 µL DNA 10 ng/µL in TE. PCR was performed with a MastercyclerProS (Eppendorf) under the following conditions: denaturation at 95 °C for 2 minutes followed by 45 cycles of 95 °C for 30 seconds, 56 °C for 30 seconds, and 72 °C for 1 minute, followed by 72 °C for 5 minutes. The PCR products were treated with a cocktail of 1.53 μL H2O, 0.17μL 10× SAP Buffer and 0.3μL Shrimp Alkaline Phosphatase (1.7U/μL) (SAP) (Sequenom) in a thermal cycler at 37 °C for 40 minutes followed by 85 °C for 5 minutes. The extend PCR contained 7 μL SAP treated PCR products, 0.62 μLH2O, 0.2 μL 10x iPLEX buffer, 0.2 μL 10x Termination Mix, 0.041 μLThermoSequenase (5 U/μL) and 0.94 μL of the multiplexed extend primer mix. The extend PCR was performed in a thermal cycler under the following conditions: denaturation at 95 °C for 30 seconds followed by 40 total cycles of 95 °C for 5 seconds, 52 °C for 5 seconds, 80 °C for 5 seconds (the 52 and 80 °C steps were repeated 5 times), followed by 72 °C for 3 minutes. A total of 41 μL of molecular grade water and ion exchange resin (Sequenom) was added to each sample. The plate was rotated for approximately 30 minutes on a Rotator Genie (Scientific Industries) and centrifuged at 4000 rpm for 5 minutes. All samples were spotted on the SpectroCHIP II G96 (Sequenom) using the MassArrayNanodispenser (Sequenom). Results were visualized on the MassArray analyzer 4 system (Sequenom) using the autorun settings. Data was analyzed using SequenomTyper version 4.0.

Appendix 1. JAVA program used to extract size and location strings from endoscopy reports

(Separately attached text file of Java code).

Appendix 2. Individual characteristics of 93 serrated lesion samples (sample of file)