Molecular Pathology - Specialty Testing Available
Houston Methodist Diagnostic Laboratories (HMDL) offers the latest in molecular pathology testing and technology. This rapidly growing division provides both clinical and research based testing in Molecular Genetics, Molecular Microbiology/Virology, Molecular Hematology and Molecular Oncology. In addition, we have expertise in whole genome sequencing of bacteria, assisting in the identification of organisms having uncertain provenance, investigation of possible outbreaks or patient-to-patient transmission, and evaluation of unusually virulent infections.
- Molecular Genetics
Factor II (Prothrombin) Mutation (G20210A and C20209T)
Factor V Leiden Mutation
- Molecular Microbiology/Virology
Adenovirus Qualitative PCR
BK Virus Quantitative PCR
Cytomegalovirus Quantitative PCR
Epstein-Barr Virus Quantitative PCR
HCV Qualitative PCR
HCV Quantitative PCR
Herpes Simplex Virus (HSV-1 and HSV-2) Qualitative PCR
HIV Quantitative PCR
HPV Qualitative PCR and Genotyping
Mycoplasma pneumoniae Qualitative PCR
Vitreous Fluid Pathogen Panel (CMV, HSV1, HSV2, Toxoplasma, and VZV)
Whole Genome Sequencing of Bacteria
- Molecular Hematology
B Cell Clonality Assay (IgH and Igκ)
BCR-ABL t(9;22) Quantification Assay
JAK2 V617F Mutation Detection
T Cell Clonality Assay (TCRβ and TCRγ)
- Molecular Oncology
For details on specimen requirements and other testing information, please see the individual assays under our Searchable Test Catalog.
Patient’s date of birth)
Hospital or clinic identification number
Test Request Form
Send overnight by Fedex or other courier with sample tracking.
Attention: Clinical Laboratory
6565 Fannin Str., M247
Houston, TX 77030
Contact information: Laboratory Client Services
Phone: (713) 441-4411 or 1 (855) 522-3282 (LABDATA)
Fax: (713) 441-4412
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.
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.
Mutations in the gene encoding phosphatidylinositol 3-kinase (PI3K) have also been identified in all types of glial tumors. They are most frequently associated with grade II-IV tumors and confer poor prognosis. Clinical trials of inhibitors that target the PI3K/AKT/mTOR gene axis are underway.
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 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.
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 hfave 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.
Difficult to identify strains
Acid Fast Bacillus and Fungus identification
Epidemiologic studies of possible outbreaks or transmission linkage
Unidentified transmission routes