Table 2 Sporadic and inherited genetic alterations in pancreatic ductal adenocarcinoma

None

-

None

None

1

KRAS

v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

GDP/GTP binding proteins, proliferation, survival, others

12p12.1

Act

90-95%

S

Bladder, breast, leukemia, and lung

Cardiofaciocutaneous syndrome

[15, 16, 96]

CDKN2A (p16)

Cyclin-dependent kinase inhibitor 2A

Cell cycle

9p21.3

In

90%

S/I

Melanoma

FAMMM

20-34X^¶

[97, 98]

TP53

Tumor protein p53

Cell cycle, apoptosis, DNA repair, others

17p13.1

In

75%

S

Breast, colorectal, hepatocellular, others

Li-Fraumeni syndrome

[99]

SMAD4/DPC4

SMAD family member 4

TGF-β signaling, BMP signaling, development, proliferation, others

18q21.2

In

55%

S

Colorectal

Juvenile polyposis syndrome, Myhre syndrome

[26–28, 100, 101]

TGFBR1,2

Transforming growth factor, beta receptor 1, 2

TGF-β signaling, development, proliferation, others

9q22.33, 3p24.1

In

5-10%

S

Colorectal, esophageal

Loeys-Dietz syndrome

[29, 102]

ACVR1B

Activin A receptor, type IB

TGF-β signaling, development, proliferation, others

12q13.13

In

5-10%

S

Unknown

Unknown

[30]

MKK4

Mitogen-activated protein kinase kinase 4

Cell stress, JNK signaling

17p12

In

5-10%

S

Unknown

Unknown

[103]

MLL3

Myeloid/lymphoid or mixed-lineage leukemia 3

Chromatin remodeling, transcription

7q36.1

In

<10%

S

Breast, colorectal, and leukemia

[16, 104]

ARID1A/B

AT-rich interaction domain-containing protein 1A/B

Chromatin remodeling, transcription

1p36.11, 6q25.3

In

<10%

S

Breast, ovary and liver

Coffin-Siris syndrome

[16, 105, 106]

PBRM1

Polybromo 1

Chromatin remodeling, transcription

3p21.1

In

<10%

S

Kidney

[16, 106]

SMARCA4

Swi/Snf-related, matrix associated, actin-dependent regulator of chromatin, subfamily A, member 4

Chromatin remodeling, transcription

19p13.2

In

<10%

S

Lung

Coffin-Siris syndrome, rhaboid tumor predisposition syndrome

[16, 105–107]

BRCA1, BRCA2

Breast cancer 1, early onset, breast cancer 2, early onset

DNA repair, cell cycle, genome stability

17q21.31, 13q13.1

In

<10%

I

Breast, ovary and prostate

Breast cancer

3.5-10X, 2X

[34, 108, 109]

PALB2, ATM, others

Partner and localizer of BRCA2, Ataxia telangiectasia mutated

DNA repair, cell cycle, genome stability

7q34

In

<10%

I

Unknown

Familial pancreatic cancer^¥

32X (overall)

[31, 32, 35, 39, 40]

PRSS1

Protease, serine, 1 (trypsin 1)

Cell metabolism and signaling

19p13.3

In

<10%

I

None

Familial pancreatitis

50-80X

[110]

STK11/LKB1

Serine/threonine kinase 11

p53 signaling, DNA repair, apoptosis

3p22.2, 2p21

In

<10%

I

Breast, colorectal, gastroesophageal, and small bowel

Peutz-Jeghers syndrome

132X

[33, 111]

hMLH1, hMSH2, others

MutL Homolog 1, colon cancer, nonpolyposis type 2 (I), mutS homolog 2, colon cancer, nonpolyposis type 1 (I)

DNA mismatch repair

9q22.32, 9p13.3

In

<10%

I

Biliary tract, brain, colorectal, endometrial, ovarian, stomach, ureter and renal pelvis

HNPCC

[112, 113]

FANC-C, FANC-G

Fanconi anemia, complementation group C, Fanconi anemia, complementation group G

DNA stability and repair

9q22, 9p13

In

<10%

I

Unknown

Young-age-onset pancreatic cancer

[36–38]