Molecular Pathology - Specialty Testing Available

Houston Methodist Diagnostic Laboratories (HMDL) offers the latest in molecular pathology testing and technology. Our rapidly growing division specializes in both clinical and research-based testing, including:

• Molecular Genetics
• Molecular Microbiology/Virology
• Molecular Hematology
• Molecular Oncology
  
  

Additionally, our team has expertise in whole-genome sequencing of bacteria, providing valuable support in:

• Identifying organisms with uncertain provenance
• Investigating potential outbreaks or patient-to-patient transmission
• Evaluating unusually virulent infections

1. Molecular Genetics

   • Factor II (Prothrombin) Mutation (G20210A and C20209T)

   • Factor V Leiden Mutation
     
     
2. Molecular Microbiology/Virology
• Adenovirus Qualitative PCR
• BK Virus Quantitative PCR
• Chikungunya Qualitative PCR
• Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis TMA
• Cytomegalovirus Quantitative PCR
• Dengue Virus PCR
• Enterovirus Qualitative PCR
• Epstein-Barr Virus Quantitative PCR
• HBV Quantitative PCR
• HCV Genotype
• HCV Qualitative PCR
• HCV Quantitative PCR
• Herpes Simplex Virus (HSV-1 and HSV-2) Qualitative PCR
  HIV Qualitative PCR (HIVQL)
  HIV Quantitative PCR
• HPV High Risk Qualitative PCR and Genotyping
• Human Herpesvirus 6 (HHV-6) Quantitative PCR
• JC Virus Quantitative PCR
• Mycoplasma pneumoniae Qualitative PCR
• Ophthalmology Pathogen Multiplex Test (CMV, HSV1, HSV2, Toxoplasma, and VZV)
• Parvovirus Quantitative PCR
• Varicella Zoster Virus Quantitative PCR
• West Nile Virus Qualitative PCR
• Whole Genome Sequencing of Bacteria
• Zika Virus PCR
  
  
3. Molecular Hematology
• B Cell Clonality Assay (IgH and Igκ)
• BCR-ABL t(9;22) Quantitative PCR (BCRB)
  CALR Mutation Detection 
  FLT3 Internal Tandem Duplication Analysis
• JAK2 V617F Mutation Detection
  JAK2 CALR Cascade Mutation Detection
  T Cell Clonality Assay (TCRβ and TCRγ)
4. Molecular Oncology
• Next generation sequencing based assays
• Lung Cancer Test (LCAT) (ALK, RET, ROS1, MET exon 14 skipping)
• Thyroid Cancer Test (TCAT) (PPARG, RET, NTRK1, NTRK3)
• ALK Translocation
• MET exon 14 skipping
• NTRK1 and NTRK3 Translocation
• PPARG Translocation
• RET Translocation
• ROS1 Translocation
• NGS Myeloid Mutation Coverage List
  
   Gene mutation tests
•         Colorectal carcinoma test (KRAS with reflex to BRAF)
•         ERBB2-HER2 Exon 20 Test (ERBB)
•         Glial tumor test (IDH1, IDH2)
•         Non-small cell lung carcinoma test (EGFR, KRAS and PIK3CA)
•         Thyroid tumor test (BRAF, HRAS, KRAS and NRAS)
•         Microsatellite Instability Analysis (5 loci tested with reflex to BRAF)
  
  

For details on specimen requirements and other testing information, please see the individual assays under our Searchable Test Catalog.

Sample label:

Test Request Form

Shipping

Shipping Address

Contact information: Laboratory Client Services

Factor II (Prothrombin) Mutation (G20210A and C20209T)

The prothrombin G20210A gene mutation PCR test is an aid to the evaluation of patients with suspected thrombophilia. The prothrombin gene mutation is found in 18% of patients with a family history of thrombosis. It causes increased prothrombin protein synthesis, leading to increased clot formation. Heterozygotes have a two to four-fold increased risk of developing a deep venous thrombosis compared to the general population. The risk increases twenty to twenty-five times when this mutation occurs in combination with the Factor V Leiden gene mutation. The combination of the prothrombin G20210A mutation plus oral contraceptive use has a supra-additive effect. Consider genetic consultation and counseling of potentially affected family members regarding laboratory testing.

Factor V Leiden Mutation

The Factor V Leiden PCR test is an aid to the evaluation of patients with suspected thrombophilia. Factor V Leiden is a point mutation at position 1691 of the gene encoding Factor V (F5). The mutation causes an arginine to glutamine substitution at codon 506 (R506Q). The mutant protein is resistant to cleavage by activated protein C, leading to increased clot formation. It is an autosomal dominant risk factor for inherited thrombosis. Heterozygotes (2-7% of the general population) have a three to eight-fold increased risk, and homozygotes (less than 1% of the general population) have an eighteen to eighty-fold increased risk. Consider genetic consultation and counseling of potentially affected family members regarding laboratory testing.

HPV High Risk Qualitative PCR and Genotyping

The high-risk Human Papillomavirus (HPV) genotyping assay is performed using the Roche COBAS 4800 HPV Genotyping assay reagents for nucleic acid amplification and polymerase chain reaction (PCR). The assay detects HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68, which are associated with cervical cancer and precursor lesions. Cross-reactions with other HPV genotypes may occur. The results are not intended to be used as the sole means for clinical diagnosis or patient management. Results should be correlated with cytologic and histologic findings.

A “negative” result is consistent with the absence of high-risk HPV, its presence below the limit of detection, or presence of a genotype other than those listed above. A negative result does not preclude the presence of HPV infection, as results are dependent on adequate specimen collection, presence of inhibitors and sufficient DNA for detection.

A “positive” result indicates the presence of the HPV genotype listed.

For Thin Prep specimens:

Performance characteristics of the Roche COBAS 4800 HPV Genotyping assay on Thin Prep specimens were determined by Roche Diagnostics and reviewed by the FDA.

For SurePath specimens:
This test was developed and its performance characteristics determined by the Molecular Diagnostics Laboratory within Houston Methodist Hospital. It has not been cleared or approved by the FDA. The laboratory is regulated under CLIA as qualified to perform high-complexity testing. This test is used for clinical purposes. It should not be regarded as investigational or for research.

BCR-ABL T(9;22)Qualitative PCR (BCRB)

This test is designed to detect and quantify BCR-ABL fusion transcript levels resulting from the t(9:22) translocation (Philadelphia chromosome).  The BCR-ABL t(9;22) quantitative PCR is intended for the monitoring of BCR-ABL Major p210 or Minor p190 transcript levels in patients with CML and ALL. This test utilizes two assays for the quantitative reverse transcription polymerase chain reaction based measurement of the BCR-ABL t(9;22) Major p210 (e13a2, e14a2) and Minor p190 (e1a2) transcript levels in peripheral blood and bone marrow specimens.  The BCR-ABL Major p210 transcript levels are measured and quantified on the International Scale (IS).  For BCR-ABL Major negative specimens, BCR-ABL t(9;22) Minor p190 transcript quantitation will be performed.  In patients with known BCR-ABL transcript positivity, only the Major p210 or Minor p190 assay will be performed.  This test is not intended for diagnosis of CML or ALL, nor for the monitoring of rare BCR-ABL transcripts resulting from t(9;22).

BCR-ABL Major p210 results include: percent (%) IS and Molecular Reduction. 

JAK2 V617F Mutation Detection

The V617F(c.1849G>T) mutation in the JAK2 gene has been identified in the hematopoietic cells of several myeloproliferative neoplasms (MPNs), such as polycythemia vera (65%-97%), essential thrombocythemia (25%-55%), and chronic idiopathic myelofibrosis (35%-57%) (1). The mutation has been reported at a much lower frequency in some other MPN/MDSs such as chronic myelomonocytic leukemia and myelodysplastic syndromes (MDSs) (2). This mutation causes constitutive activation of JAK2 and may play a key role in the neoplastic phenotype. Allelic burden has been correlated in some studies with clinical presentation (3). A positive result for the JAK2 V617F mutation is not specific for a particular MPN diagnosis and clinicopathologic correlation is necessary in all cases. A “Not Detected” result for the JAK2 V617F mutation does not exclude the presence of a myeloproliferative neoplasm or other neoplastic process.

1. Ralovics R, Passamonti F, Buser AS, et al: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779-1790.
2. Steensma DP, Dewald GW, Lasho TL, et al: The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and the myelodysplastic syndrome. Blood 2005;106:1207-1209.
3. Vannucchi AM, Antolini E, Tefferi A, et al: Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia 2008;22:1299–1307.
   
   

Lung Cancer Test

ALK (HGNC: ALK receptor tyrosine kinase) translocations are identified in approximately 4% of non-small cell lung cancer (NSCLC). In a selected group of EGFR-negative never or light smokers, up to one in three patients may harbor an ALK translocation. Translocations involving the ALK gene predict response to tyrosine kinase receptor inhibitors in NSCLC. The ALK and ROS1 tyrosine kinase domains have a high degree of homology and thus show an overlap in response to specific inhibitors.
Shaw, et al. J Clin Oncol. 2009;27(26):4247.

RET (HGNC: RET proto-oncogene) encodes a transmembrane receptor tyrosine kinase. The ligands are glial cell line derived neurotrophic factors, such as glial cell line derived neurotrophic factor, neurturin, artemin, and persephin. Signaling is sent through multiple pro-growth pathways including RAS/MAPK and PI3K/AKT. RET translocations are identified in 1-2% of lung adenocarcinomas and predict response to tyrosine kinase receptor inhibitors in NSCLC. The most common RET fusion partner in NSCLC (75%) is KIF5B.
Rossi, et al. Thyroid. 2015;25(2):221-8 

ROS1 (HGNC: ROS proto-oncogene 1, receptor tyrosine kinase) translocations are identified in 1-2% of lung adenocarcinoma. ROS1 has a normal function as part of the insulin receptor subfamily, though a ligand has not been identified. Activation leads to signaling through MAPK and P13K pathways. Translocations involving the ROS1 gene predict response to tyrosine kinase receptor inhibitors in NSCLC. 

Bergethon, et al. J Clin Oncol. 2012 Mar;30(8):863-70.

MET (HGNC: MET proto-oncogene, receptor tyrosine kinase) is a receptor for hepatocyte growth factor (HGF). Binding of HGF, an important paracrine growth factor, leads to dimerization of MET and activation of PI3K-Akt, Ras-MAPK, and STAT/NFKB pathways. Targetable abnormalities include MET exon 14 skipping mutations (3% of lung adenocarcinomas). The presence of MET exon 14 skipping mutations predict responses to tyrosine kinase receptor inhibitors in NSCLC. 
Awad, et al. J Clin Oncol. 2016;34(7):721-30.

Thyroid Cancer Test

PPARG translocations are identified in approximately 25% of follicular thyroid carcinomas.
Nikiforov, et al. Thyroid. 2015;25(11):1217-23
 
RET translocations are also present in approximately 15% of papillary thyroid carcinoma, with a higher prevalence in cancers associated with radiation exposure. In thyroid cancers, RET translocation typically involve CCDC6 (60%).
Rossi, et al. Thyroid. 2015;25(2):221-8

NTRK1 and NTRK3 translocation are detected in approximately 1-2% of papillary thyroid carcinoma. NTRK3-ETV6 is seen more commonly in radiation-associated thyroid cancer (14%).
Leeman-Neill, et al. Cancer. 2014;120(6):799-807

Alk Translocation Test

ALK (HGNC: ALK receptor tyrosine kinase) translocations are identified in approximately 4% of non-small cell lung cancer (NSCLC). In a selected group of EGFR-negative never or light smokers, up to one in three patients may harbor an ALK translocation. Translocations involving the ALK gene predict response to tyrosine kinase receptor inhibitors in NSCLC. The ALK and ROS1 tyrosine kinase domains have a high degree of homology and thus show an overlap in response to specific inhibitors.
Shaw, et al. J Clin Oncol. 2009;27(26):4247

MET EXON 14 Skipping Test

MET (HGNC: MET proto-oncogene, receptor tyrosine kinase) is a receptor for hepatocyte growth factor (HGF). Binding of HGF, an important paracrine growth factor, leads to dimerization of MET and activation of PI3K-Akt, Ras-MAPK, and STAT/NFKB pathways. Targetable abnormalities include MET exon 14 skipping mutations (3% of lung adenocarcinomas). The presence of MET exon 14 skipping mutations predict responses to tyrosine kinase receptor inhibitors in NSCLC.
Awad, et al. J Clin Oncol. 2016;34(7):721-30.

NTRK1 and NTRK3 Translocation Test

NTRK1 and NTRK3 translocation are detected in approximately 1-2% of papillary thyroid carcinoma. NTRK3-ETV6 is seen more commonly in radiation-associated thyroid cancer (14%).
Leeman-Neill, et al. Cancer. 2014;120(6):799-807

PPARG Translocation Test

PPARG translocations are identified in approximately 25% of follicular thyroid carcinomas.
Nikiforov, et al. Thyroid. 2015;25(11):1217-23

RET Translocation Test

RET (HGNC: RET proto-oncogene) encodes a transmembrane receptor tyrosine kinase. The ligands are glial cell line derived neurotrophic factors, such as glial cell line derived neurotrophic factor, neurturin, artemin, and persephin. Signaling is sent through multiple pro-growth pathways including RAS/MAPK and PI3K/AKT. RET translocations are identified in 1-2% of lung adenocarcinomas and predict response to tyrosine kinase receptor inhibitors in NSCLC. The most common RET fusion partner in NSCLC (75%) is KIF5B.
RET translocations are also present in approximately 15% of papillary thyroid carcinoma, with a higher prevalence in cancers associated with radiation exposure. In thyroid cancers, RET translocations typically involve CCDC6 (60%).
Rossi, et al. Thyroid. 2015;25(2):221-8

ROS1 Translocation Test

ROS1 (HGNC: ROS proto-oncogene 1, receptor tyrosine kinase) translocations are identified in 1-2% of lung adenocarcinoma. ROS1 has normal function as part of the insulin receptor subfamily, though a ligand has not been identified. Activation leads to signaling through MAPK and PI3K pathways. Translocations involving the ROS1 gene predict response to tyrosine kinase receptor inhibitors in NSCLC.
Bergethon, et al. J Clin Oncol. 2012 Mar;30(8):863-70.

Colorectal Carcinoma Test

Colorectal carcinoma is the third most commonly diagnosed cancer in men and women, and it is
the second leading cause of cancer deaths in the US. Prognosis depends on the stage of the cancer, presence of lymph node involvement and metastatic spread, and likelihood of complete surgical excision. Gene mutation testing on colorectal carcinomas can improve patient care by guiding use of targeted therapies.

KRAS mutations can be detected in approximately 30-40% of all patients with colorectal carcinoma. Multiple studies have shown that patients with KRAS mutations in codons 12, 13 or 61 do not benefit from anti-EGFR therapy. In contrast, 40% of patients with a wild-type KRAS sequence respond to targeted therapies. Both the American Society for Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) have recommended that all patients with metastatic colorectal carcinoma in whom EGFR antagonists are being considered should be tested for KRAS mutational status.

BRAF mutations are identified in approximately 5% of colorectal carcinomas and are also associated with decreased response to anti-EGFR therapies.

ERBB2-HER2 EXON 20 Test

ERBB2/HER2 mutations are detected in approximately 2-4% of non-small cell lung cancers, most commonly in never smokers (less than 100 cigarettes in a patient’s lifetime) and tumors with adenocarcinoma histology. The most common mutation is an in-frame insertion within exon 20 of the gene. The exon 20 insertion leads to increased HER2 kinase activity and results in increased cell survival and tumorgenicity. In the majority of cases, ERBB2/Her2 mutations are identified in NSCLC tumors that are wildtype for EGFR mutations, ALK rearrangements, and other driver mutations. The presence of ERBB2/Her2 exon 20 insertions in lung cancer is associated with primary resistance to EGFR TKI therapy and may predict sensitivity to HER2 inhibitor therapy.

Glial tumor test

Gliomas are a group of related brain tumors that are derived from glial cells. The World Health Organization (WHO) classification scheme describes three types of gliomas, including astrocytomas, oligodendrogliomas and ependymomas. Each tumor is graded on a scale of I-IV based on multiple features. Whereas grade I tumors grow slowly and can be removed by surgery, grade II and III tumors have an intermediate phenotype. In comparison, grade IV tumors are aggressive and very difficult to treat. Gene mutation testing on glial tumors can provide additional prognostic information and guide patient care.

Mutations in codon 132 of the gene encoding isocitrate dehydrogenase 1 (IDH1) and codon 172 of the homologous gene IDH2 are frequently identified in WHO grade II and III gliomas. They are also frequently present in secondary, but not primary, glioblasoma multiforme (grade IV) tumors. IDH1 and IDH2 mutations are associated with longer progression free survival and overall survival.

Non-small cell lung carcinoma test

Lung cancer is the leading cause of cancer deaths in the US and worldwide. Approximately 85% of lung cancers are non-small cell lung cancers (NSCLCs). NSCLCs are further categorized by cell type, including adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Most NSCLCs present with advanced disease that is not curable with surgery alone. Gene mutation testing on NSCLCs can improve patient care by providing prognostic information and guiding use of targeted therapies.

Mutations in the gene encoding epidermal growth factor receptor (EGFR) are identified in approximately 10-15% of NSCLCs from patients of North American or European descent and 50% of NSCLCs from patients of Asian descent. EGFR mutations are more frequent in NSCLCs having an adenocarcinoma component. Presence of an EGFR mutation predicts better response rates and progression free survival for patients treated with tyrosine kinase inhibitors that target EGFR. Of note, the T790M and other secondary mutations in EGFR exon 20 may be associated with acquired resistance to anti-EGFR therapies.

Mutations in the gene encoding Kirsten rat sarcoma viral oncogene homologue (KRAS) are identified in approximately 10-30% of NSCLCs. Although not mutually exclusive, KRAS mutations are inversely associated with the presence of EGFR mutations and ALK gene rearrangements. Presence of a KRAS mutation predicts poor prognosis, nonresponse to adjuvant chemotherapy, and nonresponse to EGFR inhibitors.

Mutations in the gene encoding phosphatidylinositol 3-kinase (PI3K) have also been identified in all types of NSCLCs. Clinical trials of inhibitors that target the PI3K/AKT/mTOR gene axis are underway.

Thyroid tumor test

Thyroid cancer is the most common endocrine malignancy. Its incidence has steadily grown in the US over the past 10 years. Most thyroid lesions are diagnosed by cytopathological examination. However, cytomorphology reveals indeterminate features in a small proportion of cases, leading to a diagnosis of atypical cells of undetermined significance (ACUS) or follicular lesion of uncertain significance (FLUS). Gene mutation testing may guide management of thyroid lesions with an indeterminate diagnosis.

Mutations in the gene encoding BRAF are found in approximately 40-50% of papillary thyroid carcinomas (PTC). The most common mutation, BRAF V600E, may be associated with high-grade morphologic and clinical (advanced tumor stage, lymph node or distant metastases or extrathryroid extension) features. BRAF mutations have also been shown to be an independent predictor of treatment failure and tumor recurrence.

Mutations in the RAS oncogene family (HRAS, KRAS, and NRAS) can be detected in approximately 40-50% of patients with follicular thyroid carcinoma and approximately 10% of patients with PTC. Detection of a RAS mutation in a thyroid nodule provides strong evidence for neoplasia, but it does not establish the diagnosis of malignancy (74%-84% positive predictive value). The role of RAS mutations in predicting prognosis of thyroid cancer is uncertain, however it is likely that RAS-mutant follicular adenomas are precursor lesions to RAS-mutant follicular carcinomas and possibly the follicular variant of PTC. RAS mutations may also predispose well-differentiated cancers to dedifferentiate to more aggressive tumors. Testing for RAS mutations is recommended in the 2009 Revised ATA (American Thyroid Association) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer.

Microsatellite Instability Analysis

The American Cancer Society estimates that 143,000 patients are diagnosed with colorectal cancer annually in the US. Approximately 20% of cases are associated with a genetic cancer syndrome. Hereditary non-polyposis colorectal cancer (HNPCC), also termed Lynch syndrome, is the most common syndromic colorectal cancer syndrome.

Lynch syndrome has an autosomal dominant inheritance pattern. That is, a person with one or more of the characteristic gene mutations is very likely to develop Lynch syndrome. It is caused by germline mutations in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. The lifetime risk of colorectal cancer is depends on the affected gene. For example, mutations in MLH1 and MSH1 are associated with an approximate 40-80% risk, whereas mutations in PMS2 and MSH6 are associated with a 5-10% risk.

In addition to colorectal cancer, female patients with Lynch syndrome have a high risk for developing endometrial carcinoma. Tumors in the stomach, ovary, small bowel, hepatobiliary tract, and urinary tract may also occur. Clinical variants of Lynch syndrome include Muir-Torre syndrome, Turcot syndrome and constitutional MMR deficiency syndrome. Muir-Torre syndrome is associated with colorectal cancer and skin neoplasms (e.g. sebaceous carcinomas). Turcot syndrome is associated with colorectal cancer and central nervous system tumors (e.g. glioblastoma). The constitutional MMR syndrome, which is caused by biallelic mutations of MMR genes, is associated with early-onset lymphomas and brain tumors, a neurofibromatosis type-1-like pattern with cafe au lait spots, and colorectal and small bowel cancer.

The Revised Bethesda Guidelines (Umar et al, J Natl Cancer Inst, 2004) may identify patients with a personal or family history suggestive of Lynch syndrome. The criteria include early age of colorectal cancer diagnosis, tumors with a right side predominance, synchronous and metachronous colorectal cancers, and family history of colon cancer or other cancers within the spectrum of Lynch syndrome. As an alternative strategy to identify all patients with Lynch syndrome, some institutions screen all new colorectal or endometrial cancers at the time of diagnosis.

Testing for Lynch syndrome is typically performed using a combination of laboratory assays that provide complementary diagnostic information. First, microsatellite instability (MSI) is evaluated. Microsatellites are a type of repetitive DNA sequence that is unique to each person. Throughout life, the length of each microsatellite should remain stable. However, they become unstable (i.e., they change size) when the MMR genes are mutated. Our laboratory tests 5 microsatellite loci, comparing the length of each microsatellite in the tumor to the same sequence in patient-matched benign tissue. If no loci are unstable, then the result is MSI-stable. If one locus is unstable, then the result is MHI-low. If two or more microsatellite loci are unstable, then the result is MSI-high.

Detection of a MSI-H phenotype is characteristic of Lynch syndrome. However, this pattern can also occur in sporadic colorectal cancers. To help distinguish the two possibilities, our laboratory tests all MSI-H tumors for mutations in the BRAF gene. Whereas BRAF mutations are frequently detected in sporadic MSI-H tumors, they are rarely identified in Lynch syndrome cancers. If suspicion of Lynch syndrome remains high after MSI and BRAF testing, the diagnosis can be confirmed by DNA sequencing.

MSI testing can significantly improve patient care by providing key information that guides therapy. Compared to MSI-low or MSI-stable tumors, MSI-high colorectal cancers have better prognosis, lower recurrence rates and may not require adjuvant chemotherapy. MSI-high tumors may also have a better response to anti-EGFR targeted therapies since they lack BRAF mutations. However, MSI-high tumors usually do not respond to 5-fluorouracil (5-FU) monotherapy, so alternative chemotherapy regimens may be considered. The diagnosis of Lynch syndrome can also guide preventive measures for family members. Relatives of patients with Lynch syndrome may consider genetic testing for the identified MMR gene mutation. Family members may also seek colonoscopy, vaginal ultrasound, endometrial biopsy, and serum tumor marker screening more frequently or at an earlier age.

Whole Genome Sequencing of Bacteria

Utility

Technology

Compared to lower resolution molecular techniques such as 16S rDNA sequencing or multi-locus sequence typing (MLST) which rely on analysis of a single gene or a few genes, whole genome sequencing can unambiguously classify organisms and define genetic relationships (1). Whole genome sequencing has been used in the clinical laboratory for species assignment of slow growing, difficult to cultivate or difficult to identify organisms (2); near real-time investigation of nosocomial infections and possible infectious outbreaks (3); understanding bacteria strain genotype – patient disease phenotype relationships (4); and studying the molecular basis of severe, unusual or interesting infections (5).

1. Olsen, R.J., et al. "Bacterial genomics in infectious disease and the clinical pathology laboratory." Arch Pathol Lab Med 136, 1414-1422 (2012).
2. Long, S.W., et al. "A genomic day in the life of a clinical microbiology laboratory." J Clin Microbiol 51, 1272-1277 (2013).
3. Fittipaldi, N., et al. "Genomic analysis of emm59 group A Streptococcus invasive strains, United States." Emerg Infect Dis 18, 650-652 (2012).
4. Olsen, R.J., et al. "Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis." Proc Natl Acad Sci USA 107, 888-893 (2010).
5. OWright, A.M., et al. "Rapidly progressive, fatal, inhalation anthrax-like infection in a human: case report, pathogen genome sequencing, pathology, and coordinated response." Arch Pathol Lab Med 135, 1447-1459 (2011).