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  1. NGS Panel – Genetic Testing for Ovarian Cancer

Ovarian Cancer

May 07, 2018

Disease summary:

Amongst gynecological cancers, ovarian cancer is the most common cause of death in women. Familial ovarian cancer is a complex condition and one of the most common malignancies worldwide, that can be classified in several histological subtypes, characterized by specific cells of origin, clinical features, molecular compositions and treatment responses 1, 2. As 20% (1 in 5) of ovarian cancer cases are due to an inherited pathogenic variant in a cancer predisposition gene, genetic counseling and testing is recommended for every woman diagnosed with ovarian cancer. 


Autosomal dominant 

  • The number of new cases of ovarian cancer is 12.1 per 100,000 women per year 1, 3.
  • The lifetime risk of developing ovarian cancer is about 1 in 70.
  • About 1/5th of ovarian cancer cases are due to a hereditary condition.4

Major clinical symptoms 3:

Early stage ovarian cancer:

  • Pain in the lower abdomen or side
  • A feeling of fullness in the abdomen.

Later stage ovarian cancer:

  • Back, abdominal pain
  • Irregular periods
  • Increased passing of urine
  • Constipation
  • Swollen abdomen

Advanced stage ovarian cancer:

  • Constipation
  • Tiredness
  • Loss of appetite
  • Shortness of breath

Hereditary ovarian cancer should be suspected in individuals who are fulfilling one or more of the following criteria, according to the National Comprehensive Cancer Network Guidelines 16:

  • Ovarian cancer at any age
  • Family history of ovarian cancer at any age
  • Breast cancer diagnosed at or before age 50 years
  • Multiple primary breast cancers, male breast cancer or triple-negative breast cancer, particularly when diagnosed before age 60 years
  • The combination of pancreatic cancer and/or prostate cancer with breast cancer, and/or ovarian cancer
  • Breast/ovarian cancer diagnosed at any age in an individual of Ashkenazi Jewish ancestry
  • Two or more relatives with breast/ovarian cancer, one under age 50 years
  • Three or more relatives with breast/ovarian cancer at any age
  • A previously identified BRCA1 or BRCA2 pathogenic variant in the family
  • Identification of a heterozygous pathogenic variant in one of the following genes (besides BRCA1/2)(Table 1): BARD1, BRIP1, EPCAM, MLH1, MRE11A, MSH2, MSH6, NBN, PMS1, PMS2, RAD50, RAD51C, RAD51D, STK11, TP53.
  • The main treatments for ovarian cancer include risk-reducing oophorectomy, chemotherapy, hormone therapy, targeted therapy and radiation therapy.
  • Women with ovarian cancer identified to have BRCA1/2 mutations are eligible for treatment with PARP inhibitors which are FDA-approved.
  • Ovarian cysts
  • Endometriosis
  • Pelvic inflammatory disorders
  • Appendiceal, adnexal or peritoneal tumors
  • Colon, uterine or pancreatic cancer
  • Gastric adenocarcinoma
  • Ovarian torsion
  • Pelvic abscess
  • Irritable bowel syndrome
  • Ectopic pregnancy

To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for ovarian cancer using NGS Panel Genomic:

Step 1: Whole genome sequencing from a single filter card (drop of blood), covering the entire genic region (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the ovarian cancer panel. Copy Number Variants analysis derived from NGS data is also included.

Step 2: If no pathogenic variant is identified in Step 1, continue with bioinformatics analysis covering genes that are either implicated or associated with overlapping phenotype or similar pathways.   

Genetic testing for ovarian cancer is recommended to persons that show one or more of the following features:

  • History of breast/ovarian cancer   
  • Positive family history of the ovarian cancer e.g. when there are ovarian cancer in individual family members or multiple cases of breast cancer and/or ovarian cancer on the same side of the family.
  • Present endometriosis and/or inability for pregnancy
  • Use of birth control
  • Women diagnosed with epithelial ovarian, tubal, and peritoneal cancers should receive genetic counseling and be offered genetic testing, even in the absence of a family history.

Confirmation of a clinical diagnosis through genetic testing of ovarian cancer can allow for genetic counseling and may direct medical management.

The most common genes associated with ovarian cancer are BRCA1 and BRCA2 (10%-40% of hereditary ovarian cancer cases3, 6, 7). Hereditary ovarian carcinoma risk has also been attributed to MLH1, MSH2, MSH6, PMS2, EPCAM, TP53, PTEN, STK11 and other genes 14, 15, 3,  4, 7, 8. Germline pathogenic variants in ATM, CHK2, NBS1, RAD50, PALB2, BRIP1 and other genes also moderately increase breast cancer risk 3,  4, 7, 8, 14, 15


Gene OMIM (Gene) Associated diseases (OMIM) Inheritance
ABRAXAS1 611143
ATM 607585 familial breast-ovarian cancer type 2; ataxia-telangiectasia AD, AR
BARD1 601593 familial breast-ovarian cancer type 2 AD
BRCA1 113705 familial breast-ovarian cancer type 1; pancreatic cancer type 4; Fanconi anemia, complementation group S AD, AR
BRCA2 600185 familial breast-ovarian cancer type 2; Medulloblastoma; Prostate Cancer; Wilms tumor, type 1; Fanconi anemia complementation group D1; pancreatic cancer type 2 AD, AR
BRIP1 605882 familial breast-ovarian cancer type 2; Fanconi anemia of complementation group J AD
CDH1 192090 familial breast-ovarian cancer type 2; blepharocheilodontic syndrome 1; Gastric Cancer, Hereditary Diffuse; Ovarian Cancer; Prostate Cancer; endometrial cancer AD
CHEK2 604373 familial breast-ovarian cancer type 2; Prostate Cancer; Osteogenic Sarcoma; Li-Fraumeni syndrome 2 AD
DICER1 606241 Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma AD
EPCAM 185535 Diarrhea 5, with tufting enteropathy, congenital; Colorectal cancer, hereditary nonpolyposis, type 8 AR
FANCC 613899 Fanconi anemia of complementation group C AR
MEN1 613733 multiple endocrine neoplasia type 1 AD
MLH1 120436 Muir-Torre syndrome; mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-2 AD, AR
MRE11 600814 Ataxia-telangiectasia-like disorder type 1 AR
MSH2 609309 Lynch syndrome; Muir-Torre syndrome; mismatch repair cancer syndrome AD, AR
MSH6 600678 mismatch repair cancer syndrome; endometrial cancer; hereditary nonpolyposis colorectal cancer-5 AD, AR
MUTYH 604933 familial adenomatous polyposis type 2; Gastric Cancer AR
NBN 602667 Nijmegen breakage syndrome; Aplastic Anemia; Acute lymphoblastic leukemia AR
PALB2 610355 familial breast-ovarian cancer type 2; Fanconi anemia of complementation group N; Pancreatic cancer, susceptibility to, 3 AD
PMS1 600258
PMS2 600259 mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-4 AR
PTEN 601728 Cowden syndrome 1; Cowden syndrome type 2; Bannayan-Riley-Ruvalcaba syndrome; Prostate Cancer; Macrocephaly/autism syndrome; Meningioma, familial, susceptibility to AD
RAD50 604040 Nijmegen breakage syndrome-like disorder
RAD51C 602774 Fanconi anemia of complementation group O; Breast-ovarian cancer, familial, susceptibility to, 3 AR
RAD51D 602954 susceptibility to familial breast-ovarian cancer type 4
RECQL 600537
SMARCA4 603254 Rhabdoid tumor predisposition syndrome 2; mental retardation-16 AD
STK11 602216 Peutz-Jeghers syndrome; Pancreatic Cancer; Spermatocytic seminoma, somatic AD
TP53 191170 familial breast-ovarian cancer type 2; colorectal cancer; Hepatocellular Carcinoma; Glioma susceptibility 1; Li-Fraumeni syndrome 1; Osteogenic Sarcoma; Pancreatic Cancer AD
XRCC2 600375 Fanconi anemia, complementation group U AR

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance
ABRAXAS1 611143
APC 611731 colorectal cancer; Hepatocellular Carcinoma; Desmoid disease, hereditary; familial adenomatous polyposis; Gastric Cancer AD
ATM 607585 familial breast-ovarian cancer type 2; ataxia-telangiectasia AD, AR
AXIN2 604025 colorectal cancer; oligodontia-colorectal cancer syndrome AD
BAP1 603089 Tumor predisposition syndrome AD
BARD1 601593 familial breast-ovarian cancer type 2 AD
BLM 604610 Bloom syndrome AR
BMPR1A 601299 Juvenile polyposis syndrome, infantile form AD
BRCA1 113705 familial breast-ovarian cancer type 1; pancreatic cancer type 4; Fanconi anemia, complementation group S AD, AR
BRCA2 600185 familial breast-ovarian cancer type 2; Medulloblastoma; Prostate Cancer; Wilms tumor, type 1; Fanconi anemia complementation group D1; pancreatic cancer type 2 AD, AR
BRIP1 605882 familial breast-ovarian cancer type 2; Fanconi anemia of complementation group J AD
CDH1 192090 familial breast-ovarian cancer type 2; blepharocheilodontic syndrome 1; Gastric Cancer, Hereditary Diffuse; Ovarian Cancer; Prostate Cancer; endometrial cancer AD
CDK4 123829 Melanoma, Cutaneous Malignant, Susceptibility To, 3 AD
CDKN2A 600160 Malignant melanoma 2; Pancreatic cancer/melanoma syndrome AD
CHEK2 604373 familial breast-ovarian cancer type 2; Prostate Cancer; Osteogenic Sarcoma; Li-Fraumeni syndrome 2 AD
DICER1 606241 Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma AD
DIS3L2 614184 Perlman syndrome AR
EPCAM 185535 Diarrhea 5, with tufting enteropathy, congenital; Colorectal cancer, hereditary nonpolyposis, type 8 AR
FANCC 613899 Fanconi anemia of complementation group C AR
FH 136850 Leiomyomatosis and renal cell cancer; Fumarase deficiency AD, AR
FLCN 607273 colorectal cancer; Birt-Hogg-Dube syndrome; Renal carcinoma, chromophobe, somatic; primary spontaneous pneumothorax AD
GALNT12 610290 Colorectal cancer, susceptibility to, 1
HNF1B 189907 noninsulin-dependent diabetes mellitus / Diabetes mellitus type II; MODY type 5; Renal carcinoma, chromophobe, somatic AD
HOXB13 604607 Hereditary prostate cancer type 9
KIT 164920 Mast cell disease; Piebaldism; Spermatocytic seminoma, somatic; acute myeloid leukemia; gastrointestinal stromal tumor AD
MC1R 155555 oculocutaneous albinism type 2; skin/hair/eye pigmentation 2; Melanoma, cutaneous malignant, susceptibility to, 5 AR
MEN1 613733 multiple endocrine neoplasia type 1 AD
MET 164860 Hepatocellular Carcinoma; Renal cell carcinoma, papillary; deafness type 97 AD, AR
MITF 156845 Albinism, Ocular, With Sensorineural Deafness; Tietz Syndrome; Waardenburg syndrome type 2A; Melanoma, Cutaneous Malignant, Susceptibility To, 8 AD, AR
MLH1 120436 Muir-Torre syndrome; mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-2 AD, AR
MLH3 604395 colorectal cancer; endometrial cancer; Colorectal cancer, hereditary nonpolyposis, type 7 AD
MRE11 600814 Ataxia-telangiectasia-like disorder type 1 AR
MSH2 609309 Lynch syndrome; Muir-Torre syndrome; mismatch repair cancer syndrome AD, AR
MSH3 600887 endometrial cancer; Familial adenomatous polyposis 4 AR
MSH6 600678 mismatch repair cancer syndrome; endometrial cancer; hereditary nonpolyposis colorectal cancer-5 AD, AR
MUTYH 604933 familial adenomatous polyposis type 2; Gastric Cancer AR
NBN 602667 Nijmegen breakage syndrome; Aplastic Anemia; Acute lymphoblastic leukemia AR
NF1 613113 neurofibromatosis type 1; Neurofibromatosis-Noonan syndrome; Leukemia, juvenile myelomonocytic AD
NTHL1 602656 Familial adenomatous polyposis 3 AR
PALB2 610355 familial breast-ovarian cancer type 2; Fanconi anemia of complementation group N; Pancreatic cancer, susceptibility to, 3 AD
PMS1 600258
PMS2 600259 mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-4 AR
POLD1 174761 Colorectal cancer, susceptibility to type 10; MANDIBULAR HYPOPLASIA, DEAFNESS, PROGEROID FEATURES, AND LIPODYSTROPHY SYNDROME AD
POLE 174762 Colorectal cancer, susceptibility to, 12; FILS syndrome AD, AR
POT1 606478 Melanoma, cutaneous malignant, susceptibility to, 10 AD
PRSS1 276000 hereditary pancreatitis AD
PTCH1 601309 Gorlin syndrome; Holoprosencephaly-7 AD
PTEN 601728 Cowden syndrome 1; Cowden syndrome type 2; Bannayan-Riley-Ruvalcaba syndrome; Prostate Cancer; Macrocephaly/autism syndrome; Meningioma, familial, susceptibility to AD
RAD50 604040 Nijmegen breakage syndrome-like disorder
RAD51C 602774 Fanconi anemia of complementation group O; Breast-ovarian cancer, familial, susceptibility to, 3 AR
RAD51D 602954 susceptibility to familial breast-ovarian cancer type 4
RECQL 600537
RET 164761 Hirschsprung disease; familial medullary thyroid carcinoma; multiple endocrine neoplasia 2B; pheochromocytoma; multiple endocrine neoplasia 2A; congenital central hypoventilation syndrome AD
RNF43 612482 AD
SDHA 600857 mitochondrial complex II deficiency; Leigh syndrome; dilated cardiomyopathy-1GG; paragangliomas type 5 AD, AR, M
SDHAF2 613019 paragangliomas type 2 AD
SDHB 185470 paragangliomas type 4; pheochromocytoma; gastrointestinal stromal tumor; paraganglioma and gastric stromal sarcoma AD
SDHC 602413 Paragangliomas 3; gastrointestinal stromal tumor; paraganglioma and gastric stromal sarcoma AD
SDHD 602690 paragangliomas 1; pheochromocytoma; mitochondrial complex II deficiency; paraganglioma and gastric stromal sarcoma AD, AR
SMAD4 600993 Myhre syndrome; Juvenile polyposis syndrome, infantile form; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Pancreatic Cancer AD
SMARCA4 603254 Rhabdoid tumor predisposition syndrome 2; mental retardation-16 AD
STK11 602216 Peutz-Jeghers syndrome; Pancreatic Cancer; Spermatocytic seminoma, somatic AD
TGFBR2 190182 Esophageal cancer, somatic; Loeys-Dietz syndrome 2; Colorectal cancer, hereditary nonpolyposis, type 6 AD
TP53 191170 familial breast-ovarian cancer type 2; colorectal cancer; Hepatocellular Carcinoma; Glioma susceptibility 1; Li-Fraumeni syndrome 1; Osteogenic Sarcoma; Pancreatic Cancer AD
TSC1 605284 tuberous sclerosis type 1 AD
TSC2 191092 tuberous sclerosis-2 AD
VHL 608537 Renal carcinoma, chromophobe, somatic; pheochromocytoma; von Hippel-Lindau disease; Erythrocytosis, familial, 2 AD, AR
WT1 607102 Frasier syndrome; Mesothelioma, somatic; Wilms tumor, type 1; Denys-Drash syndrome; Nephrotic syndrome, type 4; Meacham syndrome AD
XRCC2 600375 Fanconi anemia, complementation group U AR
XRCC3 600675 familial breast-ovarian cancer type 2 AD